Preparation and use of medical device coatings

Abstract

Lubrication coatings for medical devices and application thereof to specific portions of catheters are described.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims the benefit of and priority to U.S. Provisional Patent Application No. 63 / 342,321, filed on May 16, 2022, the entire contents of which are incorporated herein by reference. Technical Field

[0003] Described herein are coatings for medical devices and methods of applying these coatings. Background Art

[0004] Tubular medical devices such as catheters and microcatheters are used to perform diagnostic and therapeutic intravascular interventions. Catheters are often formed from thermoplastic polymers that have high friction. These high friction forces make vascular navigation difficult. For example, when using a support catheter, friction is felt when advancing a guide catheter (or balloon catheter) over the support catheter. The greatest amount of friction is felt around the preformed (e.g., angled or "bent") portion of the inner support catheter.

[0005] A hydrophilic coating along the entire distal portion of the catheter can reduce friction but can lead to issues with reduced stability. Summary of the invention

[0006] Disclosed herein are medical device coatings and methods of making and using the same. The disclosed coatings include "lubricious" or friction-reducing coatings for medical devices, thereby improving ease of use and enabling more precise therapeutic interventions.

[0007] Applying lubricious coatings on portions of medical devices (e.g., constricted, curved, or angled portions) significantly reduces friction when, for example, a guide catheter or balloon catheter is advanced over an inner support catheter. Providing lubricious coatings on specific portions of catheters or microcatheters as described herein would be very useful and beneficial.

[0008] Therefore, by applying a lubricious coating to a specific portion / specific inflated portion of the catheter instead of the distal portion of the catheter, friction can be reduced while maintaining stability. For example, applying a lubricious coating to a specific portion of the catheter can achieve good stability and lower friction when advancing a guide catheter or a balloon catheter over the catheter.

[0009] The coatings described herein can be applied to medical devices, such as medical devices that can withstand human tissue. In some embodiments, the coatings can be applied to medical devices that are used in vivo, such as vessels or other lumens. In some embodiments, the vessel can be a blood vessel. In some embodiments, the medical device can be a catheter or a microcatheter.

[0010] In some embodiments, the coating can be synthetic and durable and lubricious. In some embodiments, the coating can be ultraviolet (UV) cured. In some embodiments, the coating can be applied to the interior, exterior, or both of the device.

[0011] Lubricious coating can reduce and / or minimize the friction between medical device (such as catheter or microcatheter) and the tube wall, thereby enhancing the trackability of medical device in the whole tube system (vasculature).In an embodiment, the surface of the catheter is modified with a lubricious coating to reduce friction and enhance the ability to propel the catheter through tortuous and distal tube systems.

[0012] In some embodiments, the coating described herein may include a single layer. In some embodiments, the coating described herein may include two layers, a base coat and a top coat. The base coat acts as a tie layer between the thermoplastic polymer surface of the catheter and the top coat. The base coat is designed to adhere to the catheter and provide a binding site for the attachment of the top coat. The top coat is designed to adhere to the base coat and provide lubricity to reduce the friction generated when the catheter moves in the tubing system.

[0013] In some embodiments, the disclosed coatings may generally include: a basecoat layer comprising a copolymer of a first monomer of tetrahydrofuran acrylate and a second monomer, wherein the second monomer comprises a functional group suitable for further derivatization and a plurality of reactive fragments; and a topcoat layer comprising a hydrophilic polymer having more than 2 reactive fragments per molecule.

[0014] Also described is a method of coating a thermoplastic surface, such as a catheter or microcatheter surface. The method may include, for example, applying a primer coating comprising a copolymer of a first monomer of tetrahydrofuran acrylate and a second monomer to the thermoplastic surface, and applying a top coating to the primer coating, wherein the top coating comprises a hydrophilic polymer.

[0015] In some embodiments, the coatings described herein are applied to one or more specific portions of an apparatus, such as a catheter. In other embodiments, the coatings described herein are applied to specific angled, constricted, or bulbous portions of a catheter. Applying the coating to a specific portion or a specific bulbous portion of a catheter can reduce friction while maintaining stability. In some embodiments, the coating is not applied to the distal end of the catheter. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] The aspects, features and advantages that can be achieved by the embodiments of the present invention will be apparent and explained from the following description of the embodiments, with reference to the accompanying drawings, in which:

[0017] FIG. 1 illustrates the use of an inner support catheter to guide a guide catheter or balloon catheter to a target location. Figure 1A The shaped portion of the inner support conduit reshaped within the aortic branch is shown. Figure 1B The inner support catheter is shown being pulled back and advanced to the desired vessel. Figure 1C A guide catheter or balloon catheter is shown being advanced over the inner supporting catheter. Figure 1D The guide catheter or balloon catheter is shown being further advanced to the target location.

[0018] FIG. 2 illustrates the use of an inner support catheter to guide a guide catheter or balloon catheter to a target location. Figure 2A The inner support catheter is shown being advanced further to the desired location to provide more support. Figure 2B A guide catheter or balloon catheter is shown being advanced to the target location.

[0019] Figure 3 An inner support catheter for guiding a procedural catheter is shown.

[0020] Figure 4 Shows Figure 3 The "wavy" shaped part of the inner support tube after being straightened.

[0021] Figure 5 The friction forces exerted on the inner lining of a guide catheter or balloon catheter are shown.

[0022] Figure 6 Shown in Figure 5 The coating of the inner support catheter was observed on a particular portion of the catheter.

[0023] Figure 7 for Figure 6 Perspective view of the coated section.

[0024] FIG. 8 shows an internal support catheter in the aortic arch. Fig. 8A An inner support catheter is shown with a coating at its distal end. Figure 8B An internal support catheter with reduced stability is shown. DETAILED DESCRIPTION

[0025] Described herein are coatings for medical devices, methods of making, applying, and using the same. In some embodiments, the coating can increase the lubricity of the medical device.

[0026] instrument

[0027] The disclosed medical devices suitable for use with the disclosed coatings may include catheters and microcatheters, such as catheters and microcatheters formed at least in part from thermoplastic polymers / materials. Thermoplastic polymers may include, for example, poly(amides), poly(ethylene terephthalate), poly(urethanes), poly(ether sulfones), poly(carbonates), poly(vinyl chloride), and copolymers and derivatives thereof.

[0028] These thermoplastic polymers can have high friction. These high friction forces make vascular navigation difficult. Therefore, the coatings described herein can increase the lubricity of the thermoplastic polymer surface.

[0029] In some embodiments, the coatings described herein may be applied to catheters, including but not limited to access catheters, support catheters, inner catheters, inner support catheters, and / or combinations thereof. In embodiments, the coatings may be applied to a unique portion or part of a catheter. In other embodiments, the coatings described herein may be applied to a contracted, angled, or bulging portion of a catheter. In some embodiments, the coatings described herein may be applied to a non-bulging portion of a catheter. In other embodiments, the coatings described herein are applied to an inner support catheter. In some embodiments, the inner support catheter may be used with a surgical catheter. Surgical catheters include but are not limited to guide catheters and / or balloon catheters. In some implementation methods, the inner support catheter may be used with one or more surgical catheters. The inner support catheter can be used to guide a balloon catheter and / or a guide catheter to a target location.

[0030] See attached figure, Figure 1A The contoured portion of the inner support conduit reshaped within the aortic branch is shown. Figure 1B The inner support catheter 10 is shown being pulled back and advanced into the desired vessel. Figure 1C A guide catheter or balloon catheter 15 is shown advanced over the inner support catheter. Figure 1D The guide catheter or balloon catheter is shown to be further advanced to the target location. In some embodiments, as Figure 1A As shown, the shaped portion of the inner support catheter can be reshaped within the aortic branch. Figure 1B As shown, the inner support catheter can be pulled back and advanced into the desired blood vessel. Figure 1C The guide catheter or balloon catheter is shown advanced over the inner support catheter. Figure 1D As shown, the guide catheter or balloon catheter is further advanced to the target location.

[0031] Figure 2A The inner support catheter 20 is shown being advanced further to the desired location to provide more support. Figure 2B The guide catheter or balloon catheter is shown being advanced to the target location. As shown, the shaped portion of the inner support catheter can be reshaped within the aortic branch. The inner support catheter can be pulled back and advanced into the desired vessel. Then, as shown in FIG. Figure 2A The inner support catheter can be advanced further to the desired location to provide more support as shown. The guide catheter or balloon catheter is then advanced to the target location, as shown in Figure 2B shown.

[0032] Figure 3 An inner support catheter for guiding a surgical catheter is shown. The circled area indicates where friction may increase. When the inner support catheter is straightened, e.g. Figure 4 As shown, the profiled portion may be wavy.

[0033] Figure 4 Shows Figure 3 The "wavy" part of the inner support catheter after being straightened.

[0034] Figure 5 The friction generated with the inner lining of the guide catheter or balloon catheter 50 is shown. To reduce friction, the coatings described herein are applied to the inner support catheter. In some embodiments, the coating is applied to a specific portion of the inner support catheter where friction is observed.

[0035] Figure 6 The catheter is shown at a specific portion (the portion at Figure 5 Friction is observed in the coating of the inner support conduit 65, while the uncoated area is shown as 60.

[0036] Figure 7 for Figure 6 A perspective view of the coated portion 70.

[0037] FIG. 8 shows an internal support catheter in the aortic arch. Fig. 8A An inner support catheter having a coating on its distal end is shown. Fig. 8A As shown, the catheter is located above the dotted line. Figure 8B An inner support catheter with reduced stability when advancing a guide catheter or balloon catheter is shown. Figure 8B The tip of the catheter is not stable because Fig. 8A In comparison, it has fallen below the dotted line.

[0038] Medical device coating

[0039] In some embodiments, the disclosed coatings may include multiple coatings, such as, for example, a primer and a topcoat. In embodiments, the primer acts as a tie layer between the thermoplastic polymer of the catheter and the topcoat. The primer is designed to adhere to the catheter and provide a binding site for the attachment of the topcoat. In embodiments, the topcoat is designed to adhere to the primer and provide lubricity to reduce the friction generated when the catheter moves in the vascular system.

[0040] In some embodiments, the primer layer comprises a polymer, which is a copolymer of a first monomer of tetrahydrofurfuryl acrylate and at least one other monomer, wherein the at least one other monomer has a functional group capable of further chemical reaction, such as a hydroxyl group, an amino group, and a carboxylic acid group. In some embodiments, at least one other monomer comprises a hydroxyl group, which may be hydroxyethyl methacrylate, hydroxyethyl acrylate, hydroxypropyl acrylate, hydroxypropyl methacrylate, hydroxybutyl acrylate, hydroxybutyl methacrylate, and combinations and derivatives thereof. In some embodiments, at least one other monomer comprises an amino group, which may be N-(3-aminopropyl) methacrylamide, 2-aminoethyl methacrylate, 2-aminoethyl methacrylamide, and combinations and derivatives thereof. In some embodiments, at least one other monomer comprises a carboxylic acid group, which may be acrylic acid, methacrylic acid, β-carboxyethyl acrylate, and combinations and derivatives thereof.

[0041] Coating preparation method

[0042] In an embodiment, to prepare the undercoat copolymer, two or more monomers and an optional initiator may be dissolved in a solvent. The solvent may be any solvent that dissolves the two or more monomers and the optional initiator. The solvent may include benzene, toluene, xylene, dimethylformamide, dimethyl sulfoxide, dioxane, 2-methyltetrahydrofuran, anisole, benzonitrile, chlorinated aromatic solvents, diisopropyl ether, diglyme, butanol, and combinations thereof.

[0043] Initiators can be used to initiate polymerization of monomers in solution. In embodiments, polymerization can be initiated by reduction oxidation, radiation, heat, or any other method known in the art. Radiation crosslinking of monomers in solution can be achieved with ultraviolet or visible light using a suitable initiator, or can be achieved with ionizing radiation (e.g., electron beam or gamma ray) without the use of an initiator. Polymerization can be achieved by applying heat, either by conventionally heating the solution using a heat source such as a heating well, or by applying infrared light to the monomers in the solution.

[0044] In some embodiments, the initiator is azobisisobutyronitrile (AIBN) or a water-soluble AIBN derivative (2,2'-azobis(2-methylpropionamidine) dihydrochloride) or 4,4'-azobis(4-cyanovaleric acid). Other initiators may include N,N,N',N'-tetramethylethylenediamine, ammonium persulfate, benzoyl peroxide, and combinations thereof, including azobisisobutyronitrile.

[0045] In some embodiments, the initiator concentration may be, for example, from about 0.25% w / w to about 2% w / w of the mass of monomer in the solution.

[0046] In some embodiments, the polymerization reaction may be conducted at an elevated temperature, such as in a range of about 65°C to about 85°C.

[0047] After the polymerization is complete, the copolymer can be recovered by precipitation in a non-solvent and drying under vacuum.

[0048] In some embodiments, the molecular weight of the resulting copolymer may be between about 15,000 g / mole and about 150,000 g / mole, or between 25,000 g / mole and 100,000 g / mole. The molecular weight may be obtained by gel permeation chromatography using polystyrene standards.

[0049] After polymerization, the reactive group is added to the copolymer by the hydroxyl, amino and / or carboxylic acid groups of the second monomer or more monomers, such as acrylate and / or methacrylate. Usually, the derivative compound is a hetero-bifunctional compound. One part reacts with the hydroxyl, amino and / or carboxylic acid groups of the copolymer. The other part is an acrylate group or a methacrylate group. Suitable derivative compounds include 2-isocyanatoethyl acrylate, 2-isocyanatoethyl methacrylate, acrylate N-hydroxysuccinimide ester, methacrylate N-hydroxysuccinimide ester, hetero-bifunctional poly (ethylene glycol) with acrylate groups and isocyanate groups, and combinations and derivatives thereof.

[0050] In an embodiment, to prepare the derivatized copolymer, the copolymer and the derivatized compound and optionally any catalyst may be dissolved in a solvent. Generally, any solvent that dissolves the components may be used. The solvent may include dimethylformamide, dimethyl sulfoxide, toluene, acetone, acetonitrile, N,N-dimethylacetamide, N-methyl-2-pyrrolidone, and combinations thereof.

[0051] In an embodiment, when the derivatizing agent is reacted with the nucleophilic groups of the primer copolymer, the molar equivalent of the derivatizing agent may be in the range of about 5% to about 80% of the available nucleophilic groups or in the range of about 10% to about 50%. The level of such derivatizing agent corresponds to a range of 4 to 50 reactive groups per molecule. In addition, in some embodiments, a Lewis base may be added as a catalyst. The Lewis base may include triethylamine and pyridine. The Lewis base may be provided at a concentration of, for example, about 1% to about 10% of the moles of the derivatizing compound added.

[0052] In embodiments, the reaction can be carried out at an elevated temperature, such as at about 30°C, 35°C, 40°C, 45°C, 50°C or higher, to form a primer layer. After derivatization is complete, the completed modified copolymer can be recovered by precipitation in a non-solvent and drying under vacuum.

[0053] In embodiments, the topcoat layer may be formed on the primer layer. The topcoat layer polymer may include a core hydrophilic polymer that is derivatized with a polymerizable group. The core hydrophilic polymer may be any naturally occurring or synthetic polymer, its derivatives, and combinations thereof. In some embodiments, the core hydrophilic polymer is at least soluble in water to some extent.

[0054] The structure of the core hydrophilic polymer can be linear or branched, including graft structures, star structures, comb structures, brush structures, and dendritic structures.

[0055] Polymers for topcoats may include, but are not limited to, naturally occurring polymers such as proteins, collagen, albumin, fibrin, elastin, polypeptides, oligonucleotides, polysaccharides, hyaluronic acid, gelatin, chitosan, alginate, cellulose, carboxymethylcellulose, hydroxymethylcellulose, hydroxypropylcellulose, and dextran.

[0056] Polymers used for the topcoat may include, but are not limited to, synthetic polymers such as poly(ethers), poly(ethylene glycol), poly(ethylene oxide), poly(propylene glycol), poly(lactams), poly(vinyl pyrrolidone), poly(acrylates), poly(urethanes), poly(anhydrides), poly(amino acids), poly(carboxylic acids), poly(amides), poly(vinyl alcohols), and poly(phosphazenes).

[0057] The molecular weight of the hydrophilic polymer may range from about 500 amu to about 100,000 amu, or from about 1,000 amu to about 40,000 amu.

[0058] Reactive groups, such as but not limited to acrylate and / or methacrylate, can be added to the polymer together with the derivative compound through any convenient reactive fragment (such as hydroxyl, amino or carboxylic acid group). In some embodiments, the derivative compound can be a hetero-bifunctional compound. One part can react with the hydroxyl, amino and / or carboxylic acid group of the copolymer. The other part can be an acrylate or methacrylate group.

[0059] In some embodiments, the derivative compound may include acryloyl chloride, methacryloyl chloride, 2-isocyanatoethyl acrylate, 2-isocyanatoethyl methacrylate, N-hydroxysuccinimide acrylate, N-hydroxysuccinimide methacrylate, hetero-bifunctional poly(ethylene glycol) having an acrylate group and an isocyanate group, combinations thereof, and derivatives thereof.

[0060] In an embodiment, to prepare the derivatized polymer, the polymer, the derivatizing compound, and the optional catalyst are dissolved in a solvent. Generally, any solvent that dissolves the topcoat polymer, the derivatizing agent, and the optional catalyst may be used. The solvent may include aromatic and chlorinated solvents, including benzene, toluene, xylene, methylene chloride, chloroform, and combinations thereof.

[0061] In embodiments, when the derivatizing agent is reacted with the reactive fragment of the topcoat polymer, the target derivatization corresponds to less than 2 groups per molecule. In addition, in some embodiments, the derivatization may include the addition of a Lewis base as a catalyst. In some embodiments, the Lewis base may be triethylamine and pyridine at a concentration of about 1% to about 10% of the moles of the derivatizing compound added.

[0062] In some embodiments, the derivatization reaction is performed at room temperature.

[0063] After derivatization is complete, the activated polymer can be recovered by precipitation in a non-solvent and drying under vacuum.

[0064] Application of base coat

[0065] In embodiments, the primer layer may be applied to a medical device surface, such as a thermoplastic material. In embodiments, a device such as a catheter is first cleaned by wiping with a solvent, for example, to remove any primary contaminants on the catheter surface. In some embodiments, the catheter is wiped with a solvent. In some embodiments, any solvent may be used provided that it does not dissolve or degrade the thermoplastic material of the catheter. Solvents may include glycol ethers, methyl ethyl ketone, chlorinated solvents, tetrahydrofuran, hexane, ethyl acetate, and acetone.

[0066] In some embodiments, after solvent cleaning, an instrument such as a catheter shaft may be plasma treated to further clean the surface of the catheter shaft. In some embodiments, the catheter is not plasma treated. Plasmas derived from various gases may be used. In some embodiments, the plasma gas may be argon and oxygen. In some embodiments, argon plasma and oxygen plasma may be used.

[0067] In an embodiment, the primer solution may include a solvent, a primer copolymer, an optional initiator, and an optional surfactant. Typically, any solvent or solvent mixture may be used, provided that the component is soluble in the solvent or solvent mixture. The solvent may include water, alcohol, glycol ethers, aromatic compounds, polar aprotic solvents, and combinations thereof. In some embodiments, the solvent may include methanol, ethanol, isopropanol, 2-ethoxyethanol, propylene glycol monomethyl ether acetate, benzene, toluene, xylene, dimethyl formamide, dimethyl sulfoxide, and combinations thereof.

[0068] The basecoat copolymer can be dissolved in a solvent at a concentration of, for example, about 0.2% w / w to about 35% w / w, about 0.2% w / w to about 40% w / w, about 0.2% w / w to about 50% w / w, about 0.5% w / w to about 35% w / w, about 0.5% w / w to about 40% w / w, about 0.5% w / w to about 50% w / w, about 1% w / w to about 35% w / w, about 1% w / w to about 40% w / w, or about 1% w / w to about 50% w / w, depending on the desired viscosity of the basecoat solution. In some embodiments, the basecoat copolymer concentration is about 15% w / w.

[0069] In some embodiments, if an initiator is included, the initiator may include a Norrish I type initiator, a Norrish II type initiator, and combinations thereof. Norrish I type or free radical photoinitiators may include benzoin derivatives, methylolbenzoin and 4-benzoyl-1,3-dioxolane derivatives, benzylketal, α,α-dialkoxyacetophenone, α-hydroxyalkylphenone, α-aminoalkylphenone, acylphosphine oxide, bisacylphosphine oxide, acylphosphine sulfide, halogenated acetophenone derivatives, or combinations thereof.In some embodiments, the Norrish I type photoinitiator may include Irgacure 2959 (2-hydroxy-4'-(2-hydroxyethoxy)-2-methylphenylpropiophenone), Irgacure 651 (benzil dimethyl ketal or 2,2-dimethoxy-1,2-diphenylethanone, Ciba-Geigy), Irgacure 184 (1-hydroxy-cyclohexyl-phenyl ketone as the active component, Ciba-Geigy), Darocur 1173 (2-hydroxy-2-methyl-1-phenylpropan-1-one as the active component, Ciba-Geigy), Irgacure 907 (2-methyl-1-[4-(methylthio)phenyl]-2-morpholinopropan-1-one, Ciba-Geigy), Irgacure 369 (2-benzyl-2-dimethylamino-1-(4-morpholinophenyl)-butan-1-one as active ingredient, Ciba-Geigy), Esacure KIP 150 (poly{2-hydroxy-2-methyl-1-[4-(1-methylvinyl)phenyl]propan-1-one}, Fratelli Lamberti), Esacure KIP 100F (blend of poly{2-hydroxy-2-methyl-1-[4-(1-methylvinyl)phenyl]propan-1-one} and 2-hydroxy-2-methyl-1-phenyl-propan-1-one, Fratelli Lamberti), Esacure KTO 46 (blend of poly{2-hydroxy-2-methyl-1-[4-(1-methylvinyl)phenyl]propan-1-one}, 2,4,6-trimethylbenzoyldiphenyl-phosphine oxide and methyl benzophenone derivative, Fratelli Lamberti), Lamberti), acylphosphine oxides (e.g., Lucirin TPO (2,4,6-trimethylbenzoyldiphenylphosphine oxide, BASF)), Irgacure 819 (bis(2,4,6-trimethylbenzoyl)-phenyl-phosphine oxide, Ciba-Geigy), Irgacure 1700 (a 25:75% blend of bis(2,6-dimethoxybenzoyl) 2,4,4-trimethyl-pentylphosphine oxide and 2-hydroxy-2-methyl-1-phenyl-propan-1-one, Ciba-Geigy), or combinations thereof.

[0070] In some embodiments, mixtures of Type I photoinitiators may be used.

[0071] In some embodiments, Norrish II type photoinitiators can also be used in the basecoat formulation. These initiators can include aromatic ketones (e.g., benzophenone), xanthone, derivatives of benzophenone (e.g., chlorobenzophenone), blends of benzophenone and benzophenone derivatives (e.g., Photocure 81, a 50 / 50 blend of 4-methyl-benzophenone and benzophenone), Michler's Ketone, Ethyl Michler's Ketone, thioxanthone and other xanthone derivatives (e.g., Quantacure ITX (isopropylthioxanthone)), benzil, anthraquinone (e.g., 2-ethylanthraquinone), coumarins, or chemical derivatives or combinations of these photoinitiators.

[0072] In some embodiments, the basecoat formulation may include a combination of a Norrish Type I initiator and a Norrish Type II initiator.

[0073] In some embodiments, the initiator concentration in the solvent may be in the range of about 0.1% w / w to about 6% w / w. In some embodiments, the initiator concentration in the solvent may be about 0.6% w / w.

[0074] The primer solution may also optionally include a surfactant. In some embodiments, any surfactant may be used. The surfactant may include sodium lauryl sulfate, Tween 20, Span 80, Triton X-100, Pluronic F68, Pluronic L-81, combinations thereof, and derivatives thereof. The optional surfactant may be dissolved in a selected solvent at a concentration of about 0.1% w / w to about 15% w / w. In some embodiments, the concentration of the surfactant is about 0.8% w / w.

[0075] In some embodiments, to apply the primer to the catheter, the desired length of the catheter is inserted into the primer solution. In embodiments, the immersion time or the amount of time the catheter spends in the primer solution is from about 0.2 minutes to about 10 minutes, from about 0.5 minutes to about 10 minutes, from about 2 minutes to about 8 minutes, from about 3 minutes to about 6 minutes, or from about 0.5 minutes to about 8 minutes. In some embodiments, the immersion time can be about 5 minutes.

[0076] In other embodiments, the primer layer may be applied by, for example, spraying, brushing, spin coating, or the like, or combinations thereof, with or without dip coating.

[0077] In some embodiments, only portions or areas of the catheter are coated. Wherein, portions of the catheter may be shielded so that the primer is not applied to the shielded areas. For example, in embodiments, the coated portion of the device may include 0.1% of the device surface area, 0.2% of the device surface area, 0.3% of the device surface area, 0.4% of the device surface area, 0.5% of the device surface area, 0.6% of the device surface area, 0.7% of the device surface area, 0.8% of the device surface area, 0.9% of the device surface area, 1% of the device surface area, 1.5% of the device surface area, 2% of the device surface area, 2.5% of the device surface area, 3% of the device surface area, 5% of the device surface area, 10% of the device surface area, 15% of the device surface area, or more.

[0078] In embodiments, the coated portion of the device may include no more than 0.1% of the surface area of ​​the device, no more than 0.2% of the surface area of ​​the device, no more than 0.3% of the surface area of ​​the device, no more than 0.4% of the surface area of ​​the device, no more than 0.5% of the surface area of ​​the device, no more than 0.6% of the surface area of ​​the device, no more than 0.7% of the surface area of ​​the device, no more than 0.8% of the surface area of ​​the device, no more than 0.9% of the surface area of ​​the device, no more than 1% of the surface area of ​​the device, no more than 1.5% of the surface area of ​​the device, no more than 2% of the surface area of ​​the device, no more than 2.5% of the surface area of ​​the device, no more than 3% of the surface area of ​​the device, no more than 5% of the surface area of ​​the device, no more than 10% of the surface area of ​​the device, no more than 15% of the surface area of ​​the device, or more.

[0079] Likewise, in embodiments, the coated portion of the device can include from about 0.1% to about 5% of the surface area of ​​the device, from about 0.2% to about 4.5% of the surface area of ​​the device, from about 0.3% to about 4% of the surface area of ​​the device, from about 0.4% to about 3.5% of the surface area of ​​the device, from about 0.5% to about 3% of the surface area of ​​the device, from about 0.6% to about 2.5% of the surface area of ​​the device, from about 0.7% to about 2% of the surface area of ​​the device, from about 0.8% to about 1.5% of the surface area of ​​the device, from about 0.9% to about 1% of the surface area of ​​the device, and the like.

[0080] In further embodiments, the coated portion of the device may include about 0.1% to about 20% of the device surface area, about 0.5% to about 15% of the device surface area, about 1% to about 10% of the device surface area, about 2% to about 9% of the device surface area, about 3% to about 8% of the device surface area, about 4% to about 6% of the device surface area, etc.

[0081] In embodiments, the coated portion of the device may include not less than 0.1% of the surface area of ​​the device, not less than 0.2% of the surface area of ​​the device, not less than 0.3% of the surface area of ​​the device, not less than 0.4% of the surface area of ​​the device, not less than 0.5% of the surface area of ​​the device, not less than 0.6% of the surface area of ​​the device, not less than 0.7% of the surface area of ​​the device, not less than 0.8% of the surface area of ​​the device, not less than 0.9% of the surface area of ​​the device, not less than 1% of the surface area of ​​the device, not less than 1.5% of the surface area of ​​the device, not less than 2% of the surface area of ​​the device, not less than 2.5% of the surface area of ​​the device, not less than 3% of the surface area of ​​the device, not less than 5% of the surface area of ​​the device, not less than 10% of the surface area of ​​the device, not less than 15% of the surface area of ​​the device, or less.

[0082] In an embodiment, the coated portion comprises discrete portions separated by non-coated portions. For example, in an embodiment, the coated portion comprises 1 discrete portion, 2 discrete portions, 3 discrete portions, 4 discrete portions, 5 discrete portions, 6 discrete portions, 7 discrete portions, 8 discrete portions, 9 discrete portions, 10 discrete portions or more.

[0083] In an embodiment, the coated portion includes at least 1 discrete portion, at least 2 discrete portions, at least 3 discrete portions, at least 4 discrete portions, at least 5 discrete portions, at least 6 discrete portions, at least 7 discrete portions, at least 8 discrete portions, at least 9 discrete portions, at least 10 discrete portions or more.

[0084] In an embodiment, the coated portion includes no more than 1 discrete portion, no more than 2 discrete portions, no more than 3 discrete portions, no more than 4 discrete portions, no more than 5 discrete portions, no more than 6 discrete portions, no more than 7 discrete portions, no more than 8 discrete portions, no more than 9 discrete portions, no more than 10 discrete portions, etc.

[0085] In embodiments, the coated portion may include an "angled," "bent," or curved portion of the device. For example, in some embodiments, the angle may include at least 10 degrees, at least 15 degrees, at least 20 degrees, at least 25 degrees, at least 30 degrees, at least 35 degrees, at least 40 degrees, at least 45 degrees, at least 50 degrees, at least 55 degrees, at least 60 degrees, at least 65 degrees, at least 70 degrees, at least 75 degrees, at least 80 degrees, at least 85 degrees, at least 90 degrees, at least 95 degrees, at least 100 degrees, at least 105 degrees, at least 110 degrees, at least 115 degrees, at least 120 degrees, at least 125 degrees, at least 130 degrees, at least 135 degrees, at least 140 degrees, at least 145 degrees, at least 150 degrees, at least 155 degrees, at least 160 degrees, at least 165 degrees, at least 170 degrees, at least 175 degrees, at least 180 degrees, degrees, at least 185 degrees, at least 190 degrees, at least 195 degrees, at least 200 degrees, at least 205 degrees, at least 210 degrees, at least 220 degrees, at least 225 degrees, at least 230 degrees, at least 235 degrees, at least 240 degrees, at least 245 degrees, at least 250 degrees, at least 255 degrees, at least 260 degrees, at least 265 degrees, at least 270 degrees, at least 275 degrees, at least 280 degrees, at least 285 degrees, at least 290 degrees, at least 295 degrees, at least 300 degrees, at least 305 degrees, at least 310 degrees, at least 315 degrees, at least 320 degrees, at least 325 degrees, at least 330 degrees, at least 335 degrees, at least 340 degrees, at least 345 degrees, at least 350 degrees, at least 355 degrees, and the like.

[0086] In further embodiments, the coated portion may include at most 10 degrees, at most 15 degrees, at most 20 degrees, at most 25 degrees, at most 30 degrees, at most 35 degrees, at most 40 degrees, at most 45 degrees, at most 50 degrees, at most 55 degrees, at most 60 degrees, at most 65 degrees, at most 70 degrees, at most 75 degrees, at most 80 degrees, at most 85 degrees, at most 90 degrees, at most 95 degrees, at most 100 degrees, at most 105 degrees, at most 110 degrees, at most 115 degrees, at most 120 degrees, at most 125 degrees, at most 130 degrees, at most 135 degrees, at most 140 degrees, at most 145 degrees, at most 150 degrees, at most 155 degrees, at most 160 degrees, at most 165 degrees, at most 170 degrees, at most 175 degrees, at most 180 degrees, at most 185 degrees, at most 0 degrees, at most 185 degrees, at most 190 degrees, at most 195 degrees, at most 200 degrees, at most 205 degrees, at most 210 degrees, at most 220 degrees, at most 225 degrees, at most 230 degrees, at most 235 degrees, at most 240 degrees, at most 245 degrees, at most 250 degrees, at most 255 degrees, at most 260 degrees, at most 265 degrees, at most 270 degrees, at most 275 degrees, at most 280 degrees, at most 285 degrees, at most 290 degrees, at most 295 degrees, at most 300 degrees, at most 305 degrees, at most 310 degrees, at most 315 degrees, at most 320 degrees, at most 325 degrees, at most 330 degrees, at most 335 degrees, at most 340 degrees, at most 345 degrees, at most 350 degrees, at most 355 degrees, etc.

[0087] In further embodiments, the coated portion may include 10 degrees, 15 degrees, 20 degrees, 25 degrees, 30 degrees, 35 degrees, 40 degrees, 45 degrees, 50 degrees, 55 degrees, 60 degrees, 65 degrees, 70 degrees, 75 degrees, 80 degrees, 85 degrees, 90 degrees, 95 degrees, 100 degrees, 105 degrees, 110 degrees, 115 degrees, 120 degrees, 125 degrees, 130 degrees, 135 degrees, 140 degrees, 145 degrees, 150 degrees, 155 degrees, 160 degrees, 165 degrees, 170 degrees, 175 degrees, 180 degrees, degrees, 185 degrees, 190 degrees, 195 degrees, 200 degrees, 205 degrees, 210 degrees, 220 degrees, 225 degrees, 230 degrees, 235 degrees, 240 degrees, 245 degrees, 250 degrees, 255 degrees, 260 degrees, 265 degrees, 270 degrees, 275 degrees, 280 degrees, 285 degrees, 290 degrees, 295 degrees, 300 degrees, 305 degrees, 310 degrees, 315 degrees, 320 degrees, 325 degrees, 330 degrees, 335 degrees, 340 degrees, 345 degrees, 350 degrees, 355 degrees, etc.

[0088] In further embodiments, the coated portion may include an angle between about 10 and 350 degrees, about 20 and 340 degrees, about 30 and 330 degrees, about 40 and 320 degrees, about 50 and 310 degrees, about 60 and 300 degrees, about 70 and 290 degrees, about 80 and 280 degrees, about 90 and 270 degrees, about 100 and 260 degrees, about 110 and 250 degrees, about 120 and 240 degrees, about 130 and 230 degrees, about 140 and 220 degrees, about 150 and 210 degrees, about 160 and 200 degrees, about 170 and 190 degrees, and the like.

[0089] Likewise, in further embodiments, the coated portion may include an angle of about 10 to 40 degrees, about 20 to 50 degrees, about 30 to 60 degrees, about 40 to 70 degrees, about 50 to 80 degrees, about 60 to 90 degrees, about 70 to 100 degrees, about 80 to 110 degrees, about 90 to 120 degrees, about 100 to 130 degrees, about 110 to 140 degrees, about 120 to 150 degrees, about 130 to 160 degrees, about 140 to 170 degrees, about 150 to 180 degrees, about 160 to 190 degrees, about 1 degrees, about 170 to 200 degrees, about 180 to 210 degrees, about 190 to 220 degrees, about 200 to 230 degrees, about 210 to 240 degrees, about 220 to 250 degrees, about 230 to 260 degrees, about 240 to 270 degrees, about 250 to 280 degrees, about 260 to 290 degrees, about 270 to 300 degrees, about 280 to 310 degrees, about 290 to 320 degrees, about 300 to 330 degrees, about 310 to 340 degrees, about 320 to 350 degrees, etc.

[0090] In embodiments, the coated portion may include a "bend" or curved portion of the device that is flanked by two straight portions. For example, in embodiments, the straight portions may be connected by bends or curved portions where the straight portions include at least 10 degrees, at least 15 degrees, at least 20 degrees, at least 25 degrees, at least 30 degrees, at least 35 degrees, at least 40 degrees, at least 45 degrees, at least 50 degrees, at least 55 degrees, at least 60 degrees, at least 65 degrees, at least 70 degrees, at least 75 degrees, at least 80 degrees, at least 85 degrees, at least 90 degrees, at least 95 degrees, at least 100 degrees, at least 105 degrees, at least 110 degrees, at least 115 degrees, at least 120 degrees, at least 125 degrees, at least 130 degrees, at least 135 degrees, at least 140 degrees, at least 145 degrees, at least 150 degrees, at least 155 degrees, at least 160 degrees, at least 165 degrees, at least 170 degrees, at least 175 degrees, at least 180 degrees, at least 185 degrees, at least 186 degrees, at least 187 degrees, at least 188 degrees, at least 190 degrees, at least 201 degrees, at least 202 degrees, at least 203 degrees, at least 204 degrees, at least 205 degrees, at least 206 degrees, at least 207 degrees An angle of at least 175 degrees, at least 180 degrees, at least 185 degrees, at least 190 degrees, at least 195 degrees, at least 200 degrees, at least 205 degrees, at least 210 degrees, at least 220 degrees, at least 225 degrees, at least 230 degrees, at least 235 degrees, at least 240 degrees, at least 245 degrees, at least 250 degrees, at least 255 degrees, at least 260 degrees, at least 265 degrees, at least 270 degrees, at least 275 degrees, at least 280 degrees, at least 285 degrees, at least 290 degrees, at least 295 degrees, at least 300 degrees, at least 305 degrees, at least 310 degrees, at least 315 degrees, at least 320 degrees, at least 325 degrees, at least 330 degrees, at least 335 degrees, at least 340 degrees, at least 345 degrees, at least 350 degrees, at least 355 degrees, etc.

[0091] In further embodiments, the straight portions may include at most 10 degrees, at most 15 degrees, at most 20 degrees, at most 25 degrees, at most 30 degrees, at most 35 degrees, at most 40 degrees, at most 45 degrees, at most 50 degrees, at most 55 degrees, at most 60 degrees, at most 65 degrees, at most 70 degrees, at most 75 degrees, at most 80 degrees, at most 85 degrees, at most 90 degrees, at most 95 degrees, at most 100 degrees, at most 105 degrees, at most 110 degrees, at most 115 degrees, at most 120 degrees, at most 125 degrees, at most 130 degrees, at most 135 degrees, at most 140 degrees, at most 145 degrees, at most 150 degrees, at most 155 degrees, at most 160 degrees, at most 165 degrees, at most 170 degrees, at most 175 degrees, at most 180 degrees, at most 185 degrees, at most 186 degrees, at most 187 degrees, at most 188 degrees, at most 189 degrees, at most 190 degrees 80 degrees, up to 185 degrees, up to 190 degrees, up to 195 degrees, up to 200 degrees, up to 205 degrees, up to 210 degrees, up to 220 degrees, up to 225 degrees, up to 230 degrees, up to 235 degrees, up to 240 degrees, up to 245 degrees, up to 250 degrees, up to 255 degrees, up to 260 degrees, up to 265 degrees, up to 270 degrees , up to 275 degrees, up to 280 degrees, up to 285 degrees, up to 290 degrees, up to 295 degrees, up to 300 degrees, up to 305 degrees, up to 310 degrees, up to 315 degrees, up to 320 degrees, up to 325 degrees, up to 330 degrees, up to 335 degrees, up to 340 degrees, up to 345 degrees, up to 350 degrees, up to 355 degrees, etc.

[0092] In further embodiments, the straight portions may include 10 degrees, 15 degrees, 20 degrees, 25 degrees, 30 degrees, 35 degrees, 40 degrees, 45 degrees, 50 degrees, 55 degrees, 60 degrees, 65 degrees, 70 degrees, 75 degrees, 80 degrees, 85 degrees, 90 degrees, 95 degrees, 100 degrees, 105 degrees, 110 degrees, 115 degrees, 120 degrees, 125 degrees, 130 degrees, 135 degrees, 140 degrees, 145 degrees, 150 degrees, 155 degrees, 160 degrees, 165 degrees, 170 degrees, 175 degrees, 180 degrees, 185 degrees, 190 degrees, 200 degrees, 200 degrees, 200 degrees, 200 degrees, 200 degrees, 200 degrees, 200 degrees, 200 degrees, 200 degrees Angles of 0 degrees, 185 degrees, 190 degrees, 195 degrees, 200 degrees, 205 degrees, 210 degrees, 220 degrees, 225 degrees, 230 degrees, 235 degrees, 240 degrees, 245 degrees, 250 degrees, 255 degrees, 260 degrees, 265 degrees, 270 degrees, 275 degrees, 280 degrees, 285 degrees, 290 degrees, 295 degrees, 300 degrees, 305 degrees, 310 degrees, 315 degrees, 320 degrees, 325 degrees, 330 degrees, 335 degrees, 340 degrees, 345 degrees, 350 degrees, 355 degrees, etc.

[0093] In further embodiments, the straight portions may include angles between about 10 and 350 degrees, about 20 and 340 degrees, about 30 and 330 degrees, about 40 and 320 degrees, about 50 and 310 degrees, about 60 and 300 degrees, about 70 and 290 degrees, about 80 and 280 degrees, about 90 and 270 degrees, about 100 and 260 degrees, about 110 and 250 degrees, about 120 and 240 degrees, about 130 and 230 degrees, about 140 and 220 degrees, about 150 and 210 degrees, about 160 and 200 degrees, about 170 and 190 degrees, etc., relative to each other.

[0094] Likewise, in further embodiments, the straight portions may include angles between about 10 and 40 degrees, about 20 and 50 degrees, about 30 and 60 degrees, about 40 and 70 degrees, about 50 and 80 degrees, about 60 and 90 degrees, about 70 and 100 degrees, about 80 and 110 degrees, about 90 and 120 degrees, about 100 and 130 degrees, about 110 and 140 degrees, about 120 and 150 degrees, about 130 and 160 degrees, about 140 and 170 degrees, about 150 and 180 degrees, about 160 and 190 degrees. between about 0 degrees, between about 170 and 200 degrees, between about 180 and 210 degrees, between about 190 and 220 degrees, between about 200 and 230 degrees, between about 210 and 240 degrees, between about 220 and 250 degrees, between about 230 and 260 degrees, between about 240 and 270 degrees, between about 250 and 280 degrees, between about 260 and 290 degrees, between about 270 and 300 degrees, between about 280 and 310 degrees, between about 290 and 320 degrees, between about 300 and 330 degrees, between about 310 and 340 degrees, between about 320 and 350 degrees, etc.

[0095] In an embodiment, after dipping or otherwise applying the primer, the catheter is exposed to ultraviolet radiation having a wavelength in the range of, for example, about 10 nm to about 400 nm, about 100 nm to about 400 nm, about 200 nm to about 400 nm, about 200 nm to about 300 nm, or about 300 nm to about 400 nm. Combinations of wavelengths within this range may also provide suitable primers. In an embodiment, the ultraviolet radiation may be applied at a first wavelength between about 200 nm to about 300 nm and a second wavelength between about 300 nm to about 400 nm. In an embodiment, the wavelengths may include 254 nm and 365 nm.

[0096] In an embodiment, the curing time or the amount of time the catheter is exposed to ultraviolet radiation is in the range of about 0.5 minutes to about 10 minutes, in the range of about 1 minute to about 10 minutes, in the range of about 1 minute to about 8 minutes, in the range of about 0.5 minutes to about 6 minutes, in the range of about 1 minute to about 6 minutes, in the range of about 1 minute to about 3 minutes, or in the range of about 0.5 minutes to about 30 minutes. In one embodiment, the curing time is about 2 minutes.

[0097] In some embodiments, after the curing time is complete, the primer application process is complete.

[0098] Application of topcoat

[0099] In an embodiment, a topcoat can be applied to the finished primer. The topcoat solution can include a solvent, a topcoat polymer, an optional initiator, and an optional surfactant. Typically, any solvent or solvent mixture can be utilized, provided that the component is soluble in the solvent or solvent mixture. Suitable solvents can include water, alcohol, glycol ethers, aromatic compounds, polar aprotic solvents, and combinations thereof. In some embodiments, the solvent can include methanol, ethanol, isopropanol, 2-ethoxyethanol, propylene glycol monomethyl ether acetate, benzene, toluene, xylene, dimethylformamide, dimethyl sulfoxide, and combinations thereof.

[0100] In embodiments, the topcoat polymer may be dissolved in a selected solvent at a concentration of about 5% w / w to about 75% w / w, about 5% w / w to about 80% w / w, about 5% w / w to about 90% w / w, about 10% w / w to about 80% w / w, about 10% w / w to about 75% w / w, about 5% w / w to about 50% w / w, about 5% w / w to about 40% w / w, about 5% w / w to about 40% w / w, about 20% w / w to about 40% w / w, about 20% w / w to about 30% w / w, depending on the desired viscosity of the topcoat solution. In one embodiment, the topcoat polymer concentration is about 25% w / w.

[0101] In an embodiment, the optional initiator may include a Norrish I type initiator, a Norrish II type initiator, and combinations thereof. The Norrish I type or free radical photoinitiator may include benzoin derivatives, methylolbenzoin and 4-benzoyl-1,3-dioxolane derivatives, benzylketal, α,α-dialkoxyacetophenone, α-hydroxyalkylphenone, α-aminoalkylphenone, acylphosphine oxide, bisacylphosphine oxide, acylphosphine sulfide, halogenated acetophenone derivatives, and the like. Norrish I type photoinitiators may include Irgacure 2959 (2-hydroxy-4'-(2-hydroxyethoxy)-2-methylpropiophenone), Irgacure 651 (benzil dimethyl ketal or 2,2-dimethoxy-1,2-diphenylethanone, Ciba-Geigy), Irgacure 184 (1-hydroxy-cyclohexyl-phenyl ketone as active ingredient, Ciba-Geigy), Darocur 1173 (2-hydroxy-2-methyl-1-phenylpropan-1-one as active ingredient, Ciba-Geigy), Irgacure 907 (2-methyl-1-[4-(methylthio)phenyl]-2-morpholinopropan-1-one, Ciba-Geigy), Irgacure Esacure KTO 46 (a blend of poly{2-hydroxy-2-methyl-1-[4-(1-methylvinyl)phenyl]propan-1-one}, Fratelli Lamberti), Esacure KIP 150 (poly{2-hydroxy-2-methyl-1-[4-(1-methylvinyl)phenyl]propan-1-one}, Fratelli Lamberti), Esacure KIP100F (a blend of poly{2-hydroxy-2-methyl-1-[4-(1-methylvinyl)phenyl]propan-1-one} and 2-hydroxy-2-methyl-1-phenyl-propan-1-one, Fratelli Lamberti), Esacure KTO 46 (a blend of poly{2-hydroxy-2-methyl-1-[4-(1-methylvinyl)phenyl]propan-1-one}, 2,4,6-trimethylbenzoyldiphenylphosphine oxide and a methylbenzophenone derivative, Fratelli Lamberti), Esacure KIP ...50 (poly{2-hydroxy-2-methyl-1-[4-(1-methylvinyl)phenyl]propan-1-one}, Fratelli Lamberti), Esacure KIP 100F (a blend of poly{2-hydroxy-2-methyl-1-[4-(1-methylvinyl)phenyl]propan-1-one}, Fratelli Lamberti), Esacure KTO 46 (a Lamberti), acylphosphine oxides (e.g., Lucirin TPO (2,4,6-trimethylbenzoyldiphenylphosphine oxide, BASF)), Irgacure 819 (bis(2,4,6-trimethylbenzoyl)-phenyl-phosphine oxide, Ciba-Geigy), Irgacure 1700 (a 25:75% blend of bis(2,6-dimethoxybenzoyl) 2,4,4-trimethyl-pentylphosphine oxide and 2-hydroxy-2-methyl-1-phenyl-propan-1-one, Ciba-Geigy), etc. Mixtures of type I photoinitiators may also be used.

[0102] Norrish II type photoinitiators that may be used include aromatic ketones (e.g., benzophenone), xanthone, derivatives of benzophenone (e.g., chlorobenzophenone), blends of benzophenone and benzophenone derivatives (e.g., Photocure 81, a 50 / 50 blend of 4-methyl-benzophenone and benzophenone), Michler's ketone, ethyl Michler's ketone, thioxanthone and other xanthone derivatives (e.g., Quantacure ITX (isopropylthioxanthone)), benzil, anthraquinone (e.g., 2-ethylanthraquinone), coumarins, or chemical derivatives or combinations thereof.

[0103] In some embodiments, the topcoat formulation may include a combination of a Norrish Type I initiator and a Norrish Type II initiator.

[0104] In some embodiments, the concentration of the initiator in the solvent may be about 0.1% w / w to about 6% w / w. In some embodiments, the concentration of the initiator in the solvent may be about 0.5% w / w.

[0105] In some embodiments, the topcoat solution may also contain a surfactant. Typically, any surfactant may be used. In some embodiments, the surfactant may include sodium lauryl sulfate, Tween 20, Span 80, Triton X-100, Pluronic F68, Pluronic L-81, combinations thereof, and derivatives thereof. The optional surfactant may be dissolved in a selected solvent at a concentration of about 0.1% w / w to about 5% w / w. In some embodiments, the concentration of the surfactant is about 0.6% w / w.

[0106] In some embodiments, to apply the topcoat to the primer coated catheter, the desired length of catheter is inserted into the primer solution. In embodiments, the immersion time or the amount of time the catheter is required to be in the primer solution is from about 0.2 minutes to about 20 minutes, from about 0.5 minutes to about 20 minutes, from about 2 minutes to about 15 minutes, from about 3 minutes to about 15 minutes, or from about 8 minutes to about 12 minutes. In some embodiments, the immersion time can be about 10 minutes.

[0107] In other embodiments, the topcoat may be applied by spraying, brushing, spin coating, or the like, or combinations thereof, with or without dip coating.

[0108] In some embodiments, only portions of the catheter are coated with the topcoat, wherein portions of the catheter may be masked such that the topcoat is not applied to the masked areas.

[0109] In an embodiment, after dipping or otherwise applying the topcoat, the catheter is exposed to ultraviolet radiation having a wavelength in the range of about 10 nm to about 400 nm, about 100 nm to about 400 nm, about 200 nm to about 400 nm, about 200 nm to about 300 nm, or about 300 nm to about 400 nm. Combinations of wavelengths within this range may also provide suitable primers. In an embodiment, the ultraviolet radiation may be applied by a first wavelength between about 200 nm to about 300 nm and a second wavelength between about 300 nm to about 400 nm. In an embodiment, the wavelengths may include 254 nm and 365 nm.

[0110] The topcoat cure time or the amount of time the catheter is exposed to ultraviolet radiation is in the range of about 0.5 minutes to about 4 minutes, in the range of about 1 minute to about 4 minutes, in the range of about 1 minute to about 3 minutes, in the range of about 0.5 minutes to about 3 minutes, in the range of about 1 minute to about 5 minutes, in the range of about 0.5 minutes to about 3 minutes, or in the range of about 0.5 minutes to about 50 minutes. In one embodiment, the cure time is about 2 minutes.

[0111] The coatings described herein can reduce the maximum dynamic friction [gf] when compared to an uncoated device. In some embodiments, the coating can reduce the maximum dynamic friction by, for example, about 10%, 20%, 30%, 40%, 50%, 60% or more. In other embodiments, the coating can reduce the maximum dynamic friction by about 75%.

[0112] The coatings described herein can reduce the average dynamic friction [gf] at 60 mm displacement for 100 cycles when compared to an uncoated device. In some embodiments, the coating can reduce the maximum dynamic friction by, for example, about 10%, 20%, 30%, 40%, 50%, 60%, or more. In other embodiments, the coating can reduce the maximum dynamic friction by about 75%.

[0113] The coatings described herein can improve lubricity compared to uncoated devices. In some embodiments, the coatings can improve lubricity by about 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, etc.

[0114] In some embodiments, the coating can improve lubricity by, for example, about at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, etc.

[0115] The coatings described herein are applied to an inner support conduit. In some embodiments, the inner support conduit may be partially coated. In other embodiments, the inner support conduit may be fully coated. In some embodiments, a portion or section of the inner support conduit is coated. The coated portion may be a spherical portion of the inner support conduit. In other embodiments, the coated portion may be a non-spherical portion of the inner support conduit. In other embodiments, a specific portion where friction is observed is coated. In some embodiments, the length of the specific portion may vary depending on the amount of friction observed.

[0116] In some embodiments, the coating is not applied to the distal portion of the catheter. For example, other devices have a coating applied to the entire distal end of the catheter, which helps reduce friction. However, when the coating is applied to the distal end of the inner support catheter, the inner support catheter can lose position when a guide wire is advanced through the lumen or a guide catheter is advanced over the inner support catheter. The coating at the distal end of the inner support catheter helps reduce friction, but stability is also reduced. Therefore, the coating described herein applied to a specific portion of the inner support catheter can reduce friction without reducing stability.

[0117] The coatings described herein can be applied to a specific portion of a catheter. In some embodiments, the specific portion can be a specific portion where friction is observed. In other embodiments, the specific portion can be the proximal end of the catheter. In some embodiments, the specific portion can be located at a constricted, angled, or bulging region / portion of the catheter.

[0118] In some embodiments, a method of applying a coating to a characteristic portion of a catheter is described, wherein the coating comprises a primer and a topcoat, wherein the primer comprises a copolymer of a first monomer of tetrahydrofuran acrylate and a second monomer, wherein the second monomer comprises a functional group that can be further derivatized and a plurality of reactive fragments, and wherein the topcoat comprises a hydrophilic polymer, wherein each molecule of the hydrophilic polymer comprises more than two reactive fragments. In other embodiments, a method of applying a coating to a bulging portion of an inner support catheter is described, wherein the coating comprises a primer and a topcoat, wherein the primer comprises a copolymer of a first monomer of tetrahydrofuran acrylate and a second monomer, wherein the second monomer comprises a functional group that can be further derivatized and a plurality of reactive fragments, and wherein the topcoat comprises a hydrophilic polymer, wherein each molecule of the hydrophilic polymer comprises more than two reactive fragments.

[0119] Example 1

[0120] Preparation of basecoat polymer

[0121] To a 1 L round bottom flask was added 80.0 g of tetrahydrofurfuryl acrylate, 18.5 g of 4-hydroxybutyl acrylate and 250 mL of toluene. The solution was degassed by purging argon for 30 minutes. Then, 1.0 g of AIBN initiator was added and the mixture was purged with argon for another 10 minutes. The flask was immersed in an 80 ° C oil bath and a reflux condenser attached with an argon inlet. The mixture was heated under argon for 16 hours. The reaction was cooled and precipitated with 1.2 L of cold MTBE, and the precipitated product, a viscous polymer, was collected and dried under vacuum. Typical yields are 85-95%.

[0122] The dried polymer was dissolved in dry DMF (200 mL, about 0.5 g / mL) and treated with 0.84 mL triethylamine and 3.0 mL ethyl isocyanate acrylate. The mixture was heated to 45° C. for 5 hours. The polymer was precipitated with 1.2 L cold MTBE, washed with 2×200 mL of MTBE, and dried under high vacuum.

[0123] Example 2

[0124] Preparation of liquid basecoat solution

[0125] In a suitable container, 6.75 g of the polymer of Example 1 was dissolved in 45.0 mL of propylene glycol monomethyl ether acetate. Then, 0.34 g of Pluronic L-81 surfactant, 135 mg of benzophenone, and 135 mg of 1-hydroxycyclohexyl phenyl ketone were added. Shake for 30 minutes to achieve complete dissolution, resulting in a clear, homogeneous solution.

[0126] Example 3

[0127] Coating the microcatheters with the primer solution

[0128] A 12 inch long (0.027" outer diameter) microcatheter segment having an outer surface composed of Grilamid L25 was prepared for coating by first inserting a close fitting stainless steel mandrel into the hollow lumen and then wiping the outer surface with acetone. The microcatheter segment was then plasma treated with argon plasma (365 sccm, 300 watts, 500 mTorr) and then oxygen plasma (120 sccm, 150 watts, 400 mTorr). The liquid primer formulation prepared in Example 2 was transferred to a glass tube (12" long, 0.22" inner diameter) with a stoppered bottom. The microcatheter segment was then placed in the coating solution in the glass tube and allowed to remain for 5 minutes. The microcatheter segment was removed and immediately irradiated with UV radiation (254 nm λ, 1.3 J / cm 2 The primer was cured within 2 minutes with a UV dose of 100% UV to polymerize the primer onto the Grilamid substrate.

[0129] Example 4

[0130] Preparation of topcoat macromonomers

[0131] Fifty (50) grams of polyethylene glycol (PEG) (Mw is 4000) were dried by azeotropic distillation with toluene. A solution of PEG in 250 mL of toluene was treated with 30 mL of dichloromethane, followed by the addition of 7.0 mL of triethylamine and 4.04 mL of acryloyl chloride. The reaction mixture was stirred for 5 hours, then the precipitated salts were filtered out and the topcoat macromonomer was isolated by precipitation from 1 L of cold MTBE. The solid was isolated by filtration, washed with an additional 200 mL of MTBE, and dried overnight under high vacuum.

[0132] Example 5

[0133] Preparation of topcoat solution

[0134] In a container, 9.0 g of polyethylene glycol diacrylate (Mw 4,000) prepared in Example 4 was dissolved in 45.0 mL of methanol under shaking. Then, 0.23 g of Pluronic L-81 surfactant, 90 mg of benzophenone and 90 mg of 1-hydroxycyclohexyl phenyl ketone were added. Heat at 55° C. for 2 minutes to completely dissolve, thereby obtaining a clear, uniform solution.

[0135] Example 6

[0136] Coating the microcatheter with the topcoat solution

[0137] The topcoat solution prepared in Example 5 was transferred to a glass tube with a stoppered bottom, and the microcatheter segment with the basecoat from Example 3 was placed in the glass tube and allowed to remain in the topcoat solution for 10 minutes. The microcatheter segment was then removed and immediately irradiated with UV radiation (254 nm λ, 1.3 J / cm 2 The topcoat was cured within 2 minutes with a UV dose of 100% to polymerize the basecoat.

[0138] Example 7

[0139] Lubricity

[0140] The microcatheter samples prepared in Example 6 were tested using an Instron 5943 material tester equipped with a 5N static load cell to evaluate lubricity. When the length of the microcatheter sample was pulled through a hydraulic clamp (clamping force of 1 pound (lb.)) immersed in a hot (37°C) water bath containing distilled water, a mechanical clamp was connected to the load cell to clamp the top of the microcatheter sample. The test method pulled 100mm at a pulling rate of 254mm / min, and repeated the cycle 20 times for each sample, wherein one cycle was measured at the beginning of the hydraulic clamp closing on the sample at 0mm displacement. Then, the sample was pulled through the hydraulic clamp for 100mm displacement, and finally the hydraulic clamp was opened and the sample was returned to 0mm displacement. The maximum dynamic friction and the average dynamic friction at the 60mm displacement mark were measured and listed in the table below. The table includes the lubricity measurement results of the uncoated sample running 20 cycles as a comparison.

[0141]

[0142] The coating of Example 6 showed increased lubricity compared to the uncoated sample.

[0143] Disclosed Embodiments

[0144] Embodiment 1): A method for reducing the maximum dynamic friction force [gf] of a medical device, comprising:

[0145] applying a primer coating to the device;

[0146] applying a topcoat layer onto the basecoat layer;

[0147] The base coating and the top coating form a lubricated surface on the medical device, thereby reducing the maximum dynamic friction.

[0148] Embodiment 2): The method of embodiment 1, wherein the base coating and top coating are applied to at least 1% of the surface area of ​​the device.

[0149] Embodiment 3): The method of embodiment 2, wherein the base coating and top coating are applied to at least 5% of the surface area of ​​the device.

[0150] Embodiment 4): The method of embodiment 3, wherein the base coating and top coating are applied to at least 10% of the surface area of ​​the device.

[0151] Embodiment 5): The method of embodiment 2, wherein the primer layer comprises a copolymer of a first monomer of tetrahydrofuran acrylate and a second monomer.

[0152] Embodiment 6): The method of embodiment 5, wherein the second monomer comprises a hydroxyl group, an amine group, or a carboxylic acid group.

[0153] Embodiment 7): The method described in embodiment 6, wherein the second monomer includes hydroxyethyl methacrylate, hydroxyethyl acrylate, hydroxypropyl acrylate, hydroxypropyl methacrylate, hydroxybutyl acrylate, hydroxybutyl methacrylate, N-(3-aminopropyl) methacrylamide, 2-aminoethyl methacrylate, 2-aminoethyl methacrylamide, acrylic acid, methacrylic acid, β-carboxyethyl acrylate, combinations thereof or derivatives thereof.

[0154] Embodiment 8): The method of embodiment 1, wherein the top coating comprises protein, collagen, albumin, fibrin, elastin, polypeptide, oligonucleotide, polysaccharide, hyaluronic acid, gelatin, chitosan, alginate, cellulose, carboxymethyl cellulose, hydroxymethyl cellulose, hydroxypropyl cellulose, dextran, poly(ether), poly(ethylene glycol), poly(ethylene oxide), poly(propylene glycol), poly(lactam), poly(vinyl pyrrolidone), poly(acrylate), poly(urethane), poly(anhydride), poly(amino acid), poly(carboxylic acid), poly(amide), poly(vinyl alcohol) or poly(phosphazene).

[0155] Embodiment 9): The method of embodiment 1, wherein the primer is applied to an angled, constricted or bulged portion of a medical device.

[0156] Embodiment 10): The method described in embodiment 5, wherein the base coating is prepared by dissolving the copolymer and the monomer in a solvent selected from benzene, toluene, xylene, dimethylformamide, dimethyl sulfoxide, dioxane, 2-methyltetrahydrofuran, anisole, benzonitrile, chlorinated aromatic solvents, diisopropyl ether, diethylene glycol dimethyl ether, butanol, and combinations thereof.

[0157] Embodiment 11): A medical device comprising an angled, curved or constricted region, wherein the angled, curved or constricted region comprises a lubricious coating.

[0158] Embodiment 12): The medical device described in embodiment 11, wherein the two sides of the angled, curved or contracted area are straight line areas.

[0159] Embodiment 13): The medical device of embodiment 12, wherein the straight line regions form an angle of at least 10 degrees with each other.

[0160] Embodiment 14): The medical device of embodiment 13, wherein the device comprises a catheter.

[0161] Embodiment 15): The medical device of embodiment 14, wherein the straight line region comprises an angle of at least 15 degrees.

[0162] Embodiment 16): The medical device of embodiment 15, wherein the straight line region comprises an angle of at least 20 degrees.

[0163] Embodiment 17): The medical device described in embodiment 11, wherein the lubricating coating includes a primer coating.

[0164] Embodiment 18): The medical device described in embodiment 17, wherein the lubricating coating includes a top coating.

[0165] Embodiment 19): The medical device of embodiment 18, wherein the lubricating coating reduces the maximum dynamic friction [gf] of the device by 10% compared to an uncoated device. Embodiment 20): The medical device of embodiment 18, wherein the lubricating coating reduces the maximum dynamic friction [gf] of the device by 20% compared to an uncoated device. Embodiment 21): The medical device of embodiment 17, wherein the primer layer comprises a copolymer of a first monomer of tetrahydrofuran acrylate and a second monomer comprising a hydroxyl group, an amine group, or a carboxylic acid group.

[0166] Embodiment 22): The medical device of embodiment 18, wherein the top coating comprises protein, collagen, albumin, fibrin, elastin, polypeptide, oligonucleotide, polysaccharide, hyaluronic acid, gelatin, chitosan, alginate, cellulose, carboxymethyl cellulose, hydroxymethyl cellulose, hydroxypropyl cellulose, dextran, poly(ether), poly(ethylene glycol), poly(ethylene oxide), poly(propylene glycol), poly(lactam), poly(vinyl pyrrolidone), poly(acrylate), poly(urethane), poly(anhydride), poly(amino acid), poly(carboxylic acid), poly(amide), poly(vinyl alcohol) or poly(phosphazene).

[0167] Although preferred embodiments have been described in this specification and the accompanying drawings, it should be understood that many changes and modifications may occur to those skilled in the relevant art. Therefore, the scope of the present invention is not limited to the specific embodiments and examples described herein, but should be considered to include alternative embodiments and equivalents.

[0168] Unless otherwise stated, all numerals used in the specification and claims to represent the amount of components, properties (such as molecular weight), reaction conditions, etc. should be understood to be modified by the term "about" in all cases. Therefore, unless otherwise indicated, the numerical parameters listed in the specification and the appended claims are approximate values, which can change according to the desired properties sought to be obtained by the present invention. In any case, it is not intended to limit the application of the principle of equivalents of the scope of the claims, and each numerical parameter should be explained at least according to the number of significant digits reported and by applying common rounding techniques. Although the numerical range and parameters of the wide range of the present invention are approximate values, the numerical values ​​listed in the specific embodiments are reported as accurately as possible. However, any numerical value inherently contains certain errors caused by the standard deviations present in its respective corresponding test measurements.

[0169] Unless otherwise specified herein or obviously contradictory to the context, the terms "one", "the / said" and similar indicators used in the context of describing the present invention (especially in the context of the following claims) should be interpreted as covering both the singular and the plural. The description of the value range herein is intended only to be used as a shorthand method for quoting each individual value falling into the range. Unless otherwise specified herein, each individual value is incorporated into the specification as if it is quoted separately in this article. Unless otherwise specified herein or obviously contradictory to the context, all methods described herein can be carried out in any suitable order. The use of any and all examples or illustrative language (such as "for example") provided herein is only intended to better illustrate the present invention, rather than to limit the scope of the claimed invention. Any language in the specification should not be interpreted as indicating that any unclaimed element is essential for the practice of the present invention.

[0170] The grouping of the alternative elements or embodiments of the present invention disclosed herein should not be construed as limiting. Each group member can be mentioned and claimed individually or in any combination with other members in the group or other elements found herein. It is expected that one or more members in the group may be included in the group or deleted from the group for convenience and / or patentability reasons. When any such inclusion or deletion occurs, this specification is deemed to include the modified group, thereby satisfying the written description of all Markush groups used in the appended claims.

[0171] Certain embodiments of the present invention are described herein, including the best mode known to the inventor for implementing the present invention. Of course, for those of ordinary skill in the art, after reading the foregoing description, variations of the embodiments described will become apparent. The inventors hope that the technical staff will appropriately adopt such variations, and the inventors hope to practice the present invention in a manner different from that specifically described herein. Therefore, the present invention includes all modifications and equivalents of the subject matter described in the claims attached herein as allowed by applicable law. In addition, unless otherwise stated herein or clearly contradictory to the context, the present invention covers any combination of all possible variations of the above elements.

[0172] In addition, throughout the specification, numerous references have been made to patents and printed publications. The entire contents of each of the above-cited references and printed publications are individually incorporated herein by reference.

[0173] Finally, it should be understood that the embodiments of the present invention disclosed herein are illustrative of the principles of the present invention. Other modifications that may be employed are within the scope of the present invention. Therefore, by way of example and not limitation, alternative configurations of the present invention may be used according to the teachings herein. Therefore, the present invention is not limited to as specifically shown and described.

Claims

1. A method for reducing the maximum dynamic friction [gf] of a medical device, comprising: applying a primer coating to the device; applying a topcoat layer onto the basecoat layer; The base coating and the top coating form a lubricated surface on the medical device, thereby reducing the maximum dynamic friction.

2. The method of claim 1, wherein the base coating and top coating are applied to at least 1% of the surface area of ​​the device.

3. The method of claim 2, wherein the base coating and top coating are applied to at least 5% of the surface area of ​​the device.

4. The method of claim 3, wherein the base coating and top coating are applied to at least 10% of the surface area of ​​the device.

5. The method of claim 2, wherein the primer layer comprises a copolymer of a first monomer of tetrahydrofuran acrylate and a second monomer.

6. The method of claim 5, wherein the second monomer comprises a hydroxyl group, an amine group, or a carboxylic acid group.

7. The method of claim 6, wherein the second monomer comprises hydroxyethyl methacrylate, hydroxyethyl acrylate, hydroxypropyl acrylate, hydroxypropyl methacrylate, hydroxybutyl acrylate, hydroxybutyl methacrylate, N-(3-aminopropyl)methacrylamide, 2-aminoethyl methacrylate, 2-aminoethylmethacrylamide, acrylic acid, methacrylic acid, β-carboxyethyl acrylate, combinations thereof, or derivatives thereof.

8. The method of claim 1, wherein the topcoat comprises a protein, collagen, albumin, fibrin, elastin, a polypeptide, an oligonucleotide, a polysaccharide, hyaluronic acid, gelatin, chitosan, alginate, cellulose, carboxymethyl cellulose, hydroxymethyl cellulose, hydroxypropyl cellulose, dextran, a poly(ether), a poly(ethylene glycol), a poly(ethylene oxide), a poly(propylene glycol), a poly(lactam), a poly(vinyl pyrrolidone), a poly(acrylate), a poly(urethane), a poly(anhydride), a poly(amino acid), a poly(carboxylic acid), a poly(amide), a poly(vinyl alcohol), or a poly(phosphazene).

9. The method of claim 1, wherein the primer is applied to an angled, constricted, or bulged portion of the medical device.

10. The method of claim 5, wherein the primer layer is prepared by dissolving the copolymer and the monomer in a solvent selected from the group consisting of benzene, toluene, xylene, dimethylformamide, dimethyl sulfoxide, dioxane, 2-methyltetrahydrofuran, anisole, benzonitrile, chlorinated aromatic solvents, diisopropyl ether, diglyme, butanol, and combinations thereof.

11. A medical device comprising an angled, curved or constricted region, the angled, curved or constricted region comprising a lubricious coating.

12. The medical device of claim 11, wherein the angled, curved or constricted region is flanked by straight regions.

13. The medical device of claim 12, wherein the linear regions form an angle of at least 10 degrees with each other.

14. The medical device of claim 13, wherein the device comprises a catheter.

15. The medical device of claim 14, wherein the straight region comprises an angle of at least 15 degrees.

16. The medical device of claim 15, wherein the straight region comprises an angle of at least 20 degrees.

17. The medical device of claim 11, wherein the lubricious coating comprises a primer coating.

18. The medical device of claim 17, wherein the lubricious coating comprises a topcoat.

19. The medical device according to claim 18, wherein: The lubricious coating reduces the maximum dynamic friction [gf] of the device by 10% compared to an uncoated device.

20. The medical device according to claim 18, wherein: The lubricious coating reduces the maximum dynamic friction [gf] of the device by 20% compared to an uncoated device.

21. The medical device of claim 17, wherein the primer layer comprises a copolymer of a first monomer of tetrahydrofuran acrylate and a second monomer comprising a hydroxyl group, an amine group, or a carboxylic acid group.

22. The medical device of claim 18, wherein the topcoat comprises a protein, collagen, albumin, fibrin, elastin, a polypeptide, an oligonucleotide, a polysaccharide, hyaluronic acid, gelatin, chitosan, alginate, cellulose, carboxymethyl cellulose, hydroxymethyl cellulose, hydroxypropyl cellulose, dextran, a poly(ether), a poly(ethylene glycol), a poly(ethylene oxide), a poly(propylene glycol), a poly(lactam), a poly(vinyl pyrrolidone), a poly(acrylate), a poly(urethane), a poly(anhydride), a poly(amino acid), a poly(carboxylic acid), a poly(amide), a poly(vinyl alcohol), or a poly(phosphazene).

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