Manufacture and Use of Medical Device Coatings

Abstract

Lubricating coatings for medical devices and their application to specific parts of catheters are described herein.

Description

Technical Field

[0001] (Cross - Reference to Related Applications) This application claims priority based on U.S. Provisional Patent Application No. 63 / 342,321, filed on May 16, 2022, the entire content of which is incorporated herein by reference.

[0002] (Field) Described herein are coatings for medical devices and methods of applying those coatings.

Background Art

[0003] Annular medical devices such as catheters and micro - catheters are used for diagnostic and therapeutic intravascular interventions. Catheters are often formed of thermoplastic polymers with high frictional forces. These high frictional 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 friction is felt around the pre - formed (angled or "bent") portion of the inner support catheter.

[0004] A hydrophilic coating along the entire distal portion of the catheter can reduce friction but may cause problems of reduced stability.

Summary of the Invention

Problems to be Solved by the Invention

[0005] Disclosed herein are medical device coatings, as well as methods of manufacturing and using them. The disclosed coatings include "lubricating" or friction - reducing coatings for medical devices, which increase ease of use and enable more accurate therapeutic interventions.

[0006] The application of a lubricating coating to a portion of a medical device (such as a constricted, bent, or angled portion, etc.) significantly reduces the friction that occurs, for example, when advancing a guide or balloon catheter over an inner support catheter. As described herein, applying a lubricating coating to a specific portion of a catheter or microcatheter is useful and beneficial.

[0007] Thus, by applying a lubricating coating to a specific portion / specific spherical portion of the catheter and not to the distal portion of the catheter, friction is reduced while maintaining stability. For example, applying a lubricating coating to a specific portion of the catheter results in good stability and low friction when advancing a guide or balloon catheter over the catheter.

Means for Solving the Problem

[0008] The coatings described herein can be applied to medical devices such as medical devices that can be targeted at human tissues. In some embodiments, the coating can be applied to medical devices used in the body, such as in a tube or other lumen. In some embodiments, the tube is a blood vessel. In some embodiments, the medical device can be a catheter or a microcatheter.

[0009] In some embodiments, the coating is synthetic, durable, and lubricious. In some embodiments, the coating is capable of ultraviolet (UV) curing. In some embodiments, the coating can be applied to the inside, outside, or both of the device.

[0010] The lubricating coating can reduce and / or minimize the frictional force between a medical device such as a catheter or microcatheter and the tube wall, thereby enhancing the trackability of the medical device throughout the vascular system. In an embodiment, the catheter surface is improved with a lubricious coating to reduce frictional force and enhance the ability of the catheter to pass through tortuous distal blood vessels.

[0011] In some embodiments, the coatings described herein may include a single layer. In some embodiments, the coatings described herein may include two layers, for example, a base coat and a top coat. The base coat functions as a bonding 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 bonding 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 frictional forces that occur when the catheter moves within the vasculature.

[0012] In an embodiment, the disclosed coatings generally include a base coat that comprises a copolymer of a first tetrahydrofuryl acrylate monomer and a second monomer that includes a functional group that allows for further derivatization and a plurality of reactive sites, and a top coat that contains a hydrophilic polymer that includes more than two reactive sites per molecule.

[0013] Also described is a method of coating a thermoplastic surface such as the surface of a catheter or microcatheter. The method includes, for example, applying a base coat that comprises a copolymer of a first tetrahydrofuryl acrylate monomer and a second monomer to the thermoplastic surface, and applying a top coat to the base coat, the top coat containing a hydrophilic polymer.

[0014] In some embodiments, the coatings described herein are applied to a particular part(s) of a device, such as a catheter. In other embodiments, the coatings described herein are applied to a constricted or spherical part of the catheter at a particular angle. Application of the coating to a particular part or a particular spherical part of the catheter reduces friction while maintaining stability. In some embodiments, the coating is not applied to the distal end of the catheter. BRIEF DESCRIPTION OF THE DRAWINGS

[0015] Aspects, features, and advantages in which embodiments of the present invention can be realized will become apparent and will be elucidated from the following description of the embodiments with reference to the accompanying drawings.

[0016]

Figure 1A

Figure 1B

Figure 1C

Figure 1D

Figure 2A

Figure 2B

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

Figure 8A

Figure 8B

[0017] Described herein are coatings for medical devices, as well as methods of preparation, application, and use. In some embodiments, the coating can enhance the lubricity of the medical device.

[0018] (Device) Disclosed medical devices suitable for use with the disclosed coatings can include catheters and microcatheters, such as catheters and microcatheters formed at least in part of a thermoplastic polymer / material. The thermoplastic polymers can include, for example, poly(amide), poly(ethylene terephthalate), poly(urethane), poly(ether sulfone), poly(carbonate), poly(vinyl chloride), copolymers thereof, and derivatives thereof.

[0019] These thermoplastic polymers can have high frictional forces. These high frictional forces make vascular navigation difficult. Thus, the coatings described herein can enhance the lubricity of the thermoplastic polymer surface.

[0020] In some embodiments, the coatings described herein can 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 coating can be applied to a particular portion or part of the catheter. In another embodiment, the coatings described herein can be applied to constricted, angled, or spherical portions of the catheter. In some embodiments, the coatings described herein can be applied to non-spherical portions of the catheter. In another embodiment, the coatings described herein can be applied to an inner support catheter. In some embodiments, the inner support catheter can be used in combination with a treatment catheter. Treatment catheters include, but are not limited to, guide catheters, and / or balloon catheters. In some embodiments, the inner support catheter can be used in combination with one or more treatment catheters. The inner support catheter can be used to guide a balloon catheter and / or a guide catheter to a target location.

[0021] Turning to the drawings, FIG. 1A shows a shaped portion of an inner support catheter reformed within a branch of the aorta. FIG. 1B shows an inner support catheter 10 being withdrawn and advanced into a desired blood vessel. FIG. 1C shows a guide or balloon catheter 15 advanced over the inner support catheter. FIG. 1D shows the guide or balloon catheter further advanced to a target location. In some embodiments, as shown in FIG. 1A, the shaped portion of the inner support catheter can be reformed within a branch of the aorta. As shown in FIG. 1B, the inner support catheter can be withdrawn and advanced into a desired blood vessel. FIG. 1C shows a guide or balloon catheter advanced over the inner support catheter. As shown in FIG. 1D, the guide or balloon catheter is then further advanced to a target location.

[0022] Figure 2A shows an inner support catheter 20 advanced to a desired position to provide more support. Figure 2B shows a guide or balloon catheter advanced to the target position. As shown, the shaped portion of the inner support catheter can be reformed within the aortic branch. The inner support catheter can be retracted and advanced into the desired blood vessel. As shown in Figure 2A, the inner support catheter can then be further advanced to a desired position to provide more support. As shown in Figure 2B, the guide or balloon catheter is then advanced to the target position.

[0023] Figure 3 shows an inner support catheter used to guide a treatment catheter. The area enclosed by the circle indicates an area where friction may increase. When the inner support catheter is stretched straight, for example, as shown in Figure 4, the shaped portion can be wavy.

[0024] Figure 4 shows the "wave" shaped portion when the inner support catheter of Figure 3 is stretched straight.

[0025] Figure 5 shows the friction occurring against the liner inside the guide or balloon catheter 50. To reduce the friction, the coatings described herein are applied to the inner support catheter. In some embodiments, the coating is applied to specific portions where friction of the inner support catheter is observed.

[0026] Figure 6 shows the coating of the inner support catheter 65 at a specific portion of the catheter where friction was observed in Figure 5, and the uncoated area is indicated by 60.

[0027] Figure 7 shows a perspective view of the coated portion 70 of Figure 6.

[0028] Figure 8 shows an inner support catheter in the aortic arch. Figure 8A shows an inner support catheter with a coated distal end. As shown in Figure 8A, the catheter is above the dotted line. Figure 8B shows an inner support catheter with reduced stability when advancing a guide or balloon catheter. In Figure 8B, the tip of the catheter is not stable and has dropped below the dotted line compared to Figure 8A.

[0029] (Medical device coating) In some embodiments, the disclosed coating can include multiple coatings, such as, for example, a base coat and a top coat. In an embodiment, the base coat functions as a "bonding" layer between the thermoplastic polymer of the catheter and the top coat. In an embodiment, the base coat is designed to adhere to the catheter and provide a bonding site for the attachment of the top coat. In an embodiment, the top coat is designed to adhere to the base coat and provide lubricity to reduce the frictional force generated when the catheter moves within the vasculature.

[0030] In some embodiments, the base coat comprises a polymer that is a copolymer of a first tetrahydrofurfuryl acrylate monomer and at least one other monomer having a functional group capable of further chemical reactions such as hydroxyl groups, amine groups, and carboxylic acid groups. In some embodiments, at least one other monomer containing a hydroxyl group may be hydroxyethyl methacrylate, hydroxyethyl acrylate, hydroxypropyl acrylate, hydroxypropyl methacrylate, hydroxybutyl acrylate, hydroxybutyl methacrylate, combinations thereof, and derivatives thereof. In some embodiments, at least one other monomer containing an amine group may be N-(3-aminopropyl)methacrylamide, 2-aminoethyl methacrylate, 2-aminoethyl methacrylamide, combinations thereof, and derivatives thereof. In some embodiments, at least one other monomer containing a carboxylic acid may be acrylic acid, methacrylic acid, β-carboxyethyl acrylate, combinations thereof, and derivatives thereof.

[0031] (Method for preparing the coating) In an embodiment, to prepare the base coat copolymer, two or more monomers and optionally an initiator can be dissolved in a solvent. The solvent can include any solvent that dissolves two or more monomers and any initiator. The solvent can include benzene, toluene, xylene, dimethylformamide, dimethyl sulfoxide, dioxane, 2-methyltetrahydrofuran, anisole, benzonitrile, chlorinated aromatic solvents, diisopropyl ether, diglyme, butanol, and combinations thereof.

[0032] The initiator can be used to initiate the polymerization of monomers in solution. In embodiments, the polymerization can be initiated by redox, radiation, heat, or any method known in the art. The monomers in solution can be radiation cross-linked using an appropriate initiator with ultraviolet or visible light, or without an initiator with ionizing radiation (e.g., electron beam or gamma rays). The polymerization can be achieved by heating the solution in a conventional manner using a heat source such as a heating well, or by applying heat in any way by irradiating the monomers in the solution with infrared light.

[0033] 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-cyanopentanoic acid). Other initiators can include N,N,N',N'-tetramethylethylenediamine, ammonium persulfate, benzoyl peroxide, and combinations thereof including azobisisobutyronitrile.

[0034] In some embodiments, the concentration of the initiator can be, for example, from about 0.25% W / W to about 2% W / W of the mass of the monomers in the solution.

[0035] In some embodiments, the polymerization reaction can be carried out at a high temperature, such as in the range of about 65°C to about 85°C.

[0036] After the polymerization is complete, the copolymer can be recovered by precipitation in a non-solvent and dried under vacuum.

[0037] In embodiments, the resulting copolymer can have a molecular weight between about 15,000 g / mol and about 150,000 g / mol, or between 25,000 g / mol and 100,000 g / mol. This molecular weight can be determined by gel permeation chromatography using polystyrene standards.

[0038] After coincidence, reactive groups such as acrylates and / or methacrylates are added to the copolymer via the hydroxyl, amine, and / or carboxylic acid groups of the second or higher monomers. Generally, the derivatized compound is a hetero-bifunctional compound. One part reacts with the hydroxyl, amine, and / or carboxylic acid groups of the copolymer. Another part is an acrylate or methacrylate group. Suitable derivatized compounds include 2-isocyanatoethyl acrylate, 2-isocyanatoethyl methacrylate, N-hydroxysuccinimide ester of acrylic acid, N-hydroxysuccinimide ester of methacrylic acid, hetero-bifunctional poly(ethylene glycol) having acrylate groups and isocyanate groups, combinations thereof, and derivatives thereof.

[0039] In embodiments, to prepare the derivatized copolymer, the copolymer, the derivatized compound, and optionally any catalyst can be dissolved in a solvent. Generally, any solvent that dissolves the components can be used. The solvent can include dimethylformamide, dimethyl sulfoxide, toluene, acetone, acetonitrile, N,N-dimethylacetamide, N-methyl-2-pyrrolidone, and combinations thereof.

[0040] In some embodiments, when reacting the derivatized product with the nucleophilic groups of the base coat copolymer, the molar equivalent of the derivatizing agent can range from about 5% to about 80%, or about 10% to about 50%, of the available nucleophilic groups. This level of derivatized product corresponds to a range of 4 to 50 reactive groups per molecule. Further, in some embodiments, a Lewis base can be added as a catalyst. The Lewis base can include triethylamine and pyridine. The Lewis base can be provided, for example, at a concentration of about 1% to about 10% of the number of moles of the derivatized compound added.

[0041] In an embodiment, the reaction can proceed at a high temperature, such as approximately 30 °C, 35 °C, 40 °C, 45 °C, 50 °C, or even higher temperatures, to form a base coat. After the completion of derivatization, the completed modified copolymer can be recovered by precipitation in a non-solvent and dried under vacuum.

[0042] In an embodiment, a top coat can be formed on the base coat. The top coat polymer can include a hydrophilic polymer of a core derivatized with polymerizable groups. The hydrophilic polymer of the core can be any natural or synthetic polymer, their derivatives, and combinations thereof. In some embodiments, the hydrophilic polymer of the core is at least somewhat soluble in water.

[0043] The structure of the hydrophilic polymer of the core can be linear or branched, including graft, star, comb, brush, dendrimer structures.

[0044] The polymers used for the top coat can include natural polymers such as, but not limited to, proteins, collagen, albumin, fibrin, elastin, polypeptides, oligonucleotides, polysaccharides, hyaluronic acid, gelatin, chitosan, alginate, cellulose, carboxymethyl cellulose, hydroxymethyl cellulose, hydroxypropyl cellulose, and dextran.

[0045] The polymers used for the top coat can include synthetic polymers such as, but not limited to, 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), and poly(phosphazene).

[0046] The molecular weight of the hydrophilic polymer can be in the range of, for example, about 500 amu to about 100,000 amu, or about 1,000 amu to about 40,000 amu.

[0047] Although not limited, reactive groups such as acrylates and / or methacrylates can be added to the polymer via any convenient reactive moiety such as hydroxyl, amine, or carboxylic acid, together with the derivatized compound. In some embodiments, the derivatized compound can be a heterobifunctional compound. One functional moiety can react with the hydroxyl, amine, and / or carboxylic acid groups of the copolymer. The other functional moiety can be an acrylate or methacrylate group.

[0048] In some embodiments, the derivatized compound can include acryloyl chloride, methacryloyl chloride, 2-isocyanatoethyl acrylate, 2-isocyanatoethyl methacrylate, N-hydroxysuccinimide ester of acrylic acid, N-hydroxysuccinimide ester of methacrylic acid, heterobifunctional poly(ethylene glycol) having acrylate and isocyanate groups, combinations thereof, and derivatives thereof.

[0049] In embodiments, to prepare the derivatized polymer, the polymer, derivatized compound, and any catalyst are dissolved in a solvent. Generally, a solvent that dissolves the topcoat polymer, derivatizing agent, and any catalyst can be used. The solvent can include aromatic and chlorinated solvents including benzene, toluene, xylene, dichloromethane, chloroform, and combinations thereof.

[0050] In embodiments, when reacting the derivatizing agent with the reactive moiety of the topcoat polymer, the targeted derivatization corresponds to less than 2 groups per molecule. Further, in some embodiments, the derivatization can include the addition of a Lewis base as a catalyst. In some embodiments, the Lewis base can be triethylamine and pyridine at a concentration of about 1% to about 10% of the number of moles of the derivatized compound added.

[0051] In some embodiments, the derivatization reaction proceeds, for example, at room temperature.

[0052] After the derivatization is completed, the activated polymer can be recovered by precipitation in a non-solvent and dried under vacuum.

[0053] (Application of the base coat) In an embodiment, the base coat can be applied to the surface of a medical device such as a thermoplastic material. In an embodiment, first, the device such as a catheter is cleaned by wiping with a solvent to remove, for example, any large contamination from its surface. In some embodiments, the catheter is wiped with a solvent. In some embodiments, any solvent can be used as long as it does not dissolve or degrade the thermoplastic material of the catheter. The solvent can include glycol ethers, methyl ethyl ketone, chlorinated solvents, tetrahydrofuran, hexane, ethyl acetate, and acetone.

[0054] After solvent cleaning, in some embodiments, the device such as the catheter shaft can be plasma-treated to further clean its surface. In some embodiments, the catheter is not plasma-treated. Plasmas derived from various gases can be used. In some embodiments, the plasma gas can be argon and oxygen. In some embodiments, both argon and oxygen plasmas can be used.

[0055] In some embodiments, the base coat solution can include a solvent, a base coat polymer, any initiator, and any surfactant. Generally, any solvent or solvent mixture can be utilized as long as the components dissolve in the solvent or solvent mixture. The solvent can include water, alcohols, glycol ethers, aromatics, polar aprotic solvents, and combinations thereof. In some embodiments, the solvent can include methanol, ethanol, isopropyl alcohol, 2-ethoxyethanol, propylene glycol monomethyl ether acetate, benzene, toluene, xylene, dimethylformamide, dimethyl sulfoxide, and combinations thereof.

[0056] The base coat copolymer can be dissolved in a solvent at a concentration in the range 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 base coat solution. In some embodiments, the concentration of the base coat copolymer is about 15% w / w.

[0057] In some embodiments, when an initiator is included, the initiator may include Norrish type I initiators, Norrish type II initiators, and combinations thereof. Norrish type I initiators or free radical photoinitiators may include benzoin derivatives, methylol benzoin and 4-benzoyl-1,3-dioxolane derivatives, benzyl ketals, α,α-dialkoxyacetophenones, α-hydroxyalkylphenones, α-aminoalkylphenones, acylphosphine oxides, bisacylphosphine oxides, acylphosphine sulfides, halogenated acetophenone derivatives, or combinations thereof.In some embodiments, the Norrish type I photoinitiator may include acylphosphine oxides such as Irgacure 2959 (2-hydroxy-4'-(2-hydroxyethoxy)-2-methylpropiophenone), Irgacure 651 (benzyldimethylketal, or 2,2-dimethoxy-1,2-diphenylethanone, Ciba-Geigy), Irgacure 184 (1-hydroxy-cyclohexyl-phenylketone as the active ingredient, Ciba-Geigy), Darocur 1173 (2-hydroxy-2-methyl-1-phenylpropan-1-one as the active ingredient, 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 the active ingredient, Ciba-Geigy), Esacure KIP150 (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 KTO46 (a blend of poly{2-hydroxy-2-methyl-1-[4-(1-methylvinyl)phenyl]propan-1-one}, 2,4,6-trimethylbenzoyldiphenyl-phosphine oxide and a methylbenzophenone derivative, Fratelli Lamberti); 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.

[0058] In some embodiments, a mixture of type I photoinitiators can be used.

[0059] In embodiments, Norrish type II initiators can also be used in the formulation of the base coat. These initiators can include benzophenone, xanthone, derivatives of benzophenone (e.g., chlorobenzophenone), blends of benzophenone and benzophenone derivatives (e.g., Photocure 81, a 50 / 50 blend of 4-methylbenzophenone and benzophenone), Michler's ketone, ethyl Michler's ketone, thioxanthone and other xanthone derivatives such as Quantacure ITX (isopropylthioxanthone), benzyl, anthraquinone (e.g., 2-ethylanthraquinone), aromatic ketones such as coumarin, or chemical derivatives or combinations of these photoinitiators.

[0060] In some embodiments, the formulation of the base coat can include a combination of Norrish type I and Norrish type II initiators.

[0061] In embodiments, the concentration of the initiator in the solvent can range from about 0.1% to about 6% w / w. In some embodiments, the concentration of the initiator in the solvent can be about 0.6 w / w.

[0062] Also, the base coat solution can optionally include a surfactant. In some embodiments, any surfactant may be used. Surfactants can include sodium lauryl sulfate, Tween 20, Span 80, Triton X-100, Pluronic F68, Pluronic L-81, combinations thereof, and derivatives thereof. Any surfactant can be dissolved in the selected solvent at a concentration in the range 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.

[0063] In some embodiments, to apply the base coat to the catheter, the length of the catheter to be coated is placed in the base coat solution. In an embodiment, the immersion time, or the time the catheter is immersed in the base coat solution, ranges from about 0.2 to about 10 minutes, from about 0.5 to about 10 minutes, from about 2 to about 8 minutes, from about 3 to about 6 minutes, or from about 0.5 to about 8 minutes. In some embodiments, the immersion time can be about 5 minutes.

[0064] In another embodiment, the base coat can be applied by, for example, spraying, brushing, spin coating, etc., or combinations thereof with or without dip coating.

[0065] In some embodiments, only a part or region of the catheter is coated. In that case, a part of the catheter can be masked so that the base coat is not applied to the masked region. For example, in an embodiment, the coated portion of the device can include 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 1.5%, 2%, 2.5%, 3%, 5%, 10%, 15%, or more of the surface area of the device.

[0066] In an embodiment, the coated portion of the device can include 0.1% or less, 0.2% or less, 0.3% or less, 0.4% or less, 0.5% or less, 0.6% or less, 0.7% or less, 0.8% or less, 0.9% or less, 1% or less, 1.5% or less, 2% or less, 2.5% or less, 3% or less, 5% or less, 10% or less, 15% or less, or more of the surface area of the device.

[0067] Similarly, in embodiments, the portion of the device to be coated can include, among others, between about 0.1% and about 5% of the surface area of the device, between about 0.2% and about 4.5% of the surface area of the device, between about 0.3% and about 4% of the surface area of the device, between about 0.4% and about 3.5% of the surface area of the device, between about 0.5% and about 3% of the surface area of the device, between about 0.6% and about 2.5% of the surface area of the device, between about 0.7% and about 2% of the surface area of the device, between about 0.8% and about 1.5% of the surface area of the device, between about 0.9% and about 1% of the surface area of the device, etc.

[0068] In further embodiments, the portion of the device to be coated can include, among others, between about 0.1% and about 20% of the surface area of the device, between about 0.5% and about 15% of the surface area of the device, between about 1% and about 10% of the surface area of the device, between about 2% and about 9% of the surface area of the device, between about 3% and about 8% of the surface area of the device, between about 4% and about 6% of the surface area of the device, etc.

[0069] In embodiments, the portion of the device to be coated can include 0.1% or more of the surface area of the device, 0.2% or more of the surface area of the device, 0.3% or more of the surface area of the device, 0.4% or more of the surface area of the device, 0.5% or more of the surface area of the device, 0.6% or more of the surface area of the device, 0.7% or more of the surface area of the device, 0.8% or more of the surface area of the device, 0.9% or more of the surface area of the device, 1% or more of the surface area of the device, 1.5% or more of the surface area of the device, 2% or more of the surface area of the device, 2.5% or more of the surface area of the device, 3% or more of the surface area of the device, 5% or more of the surface area of the device, 10% or more of the surface area of the device, 15% or more of the surface area of the device, or less than that.

[0070] In embodiments, the portion to be coated includes discrete portions separated by portions that are not coated. For example, in embodiments, the portion to be coated includes 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 than that.

[0071] In an embodiment, the portion to be coated includes at least 1 individual portion, at least 2 individual portions, at least 3 individual portions, at least 4 individual portions, at least 5 individual portions, at least 6 individual portions, at least 7 individual portions, at least 8 individual portions, at least 9 individual portions, at least 10 individual portions, or more than that.

[0072] In an embodiment, the portion to be coated includes 1 or fewer individual portions, 2 or fewer individual portions, 3 or fewer individual portions, 4 or fewer individual portions, 5 or fewer individual portions, 6 or fewer individual portions, 7 or fewer individual portions, 8 or fewer individual portions, 9 or fewer individual portions, 10 or fewer individual portions, and the like.

[0073] In an embodiment, the portion to be coated may include an "angled", "bent", or curved portion of the device. For example, in an embodiment, the angle may be 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 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.

[0074] In a further embodiment, the portion to be coated may include angles such as up to 10 degrees, up to 15 degrees, up to 20 degrees, up to 25 degrees, up to 30 degrees, up to 35 degrees, up to 40 degrees, up to 45 degrees, up to 50 degrees, up to 55 degrees, up to 60 degrees, up to 65 degrees, up to 70 degrees, up to 75 degrees, up to 80 degrees, up to 85 degrees, up to 90 degrees, up to 95 degrees, up to 100 degrees, up to 105 degrees, up to 110 degrees, up to 115 degrees, up to 120 degrees, up to 125 degrees, up to 130 degrees, up to 135 degrees, up to 140 degrees, up to 145 degrees, up to 150 degrees, up to 155 degrees, up to 160 degrees, up to 165 degrees, up to 170 degrees, up to 175 degrees, up to 180 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.

[0075] In a further embodiment, the portion to be coated may include angles such as 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, 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.

[0076] In a further embodiment, the portion to be coated may include angles such as about 10 to 350 degrees, about 20 to 340 degrees, about 30 to 330 degrees, about 40 to 320 degrees, about 50 to 310 degrees, about 60 to 300 degrees, about 70 to 290 degrees, about 80 to 280 degrees, about 90 to 270 degrees, about 100 to 260 degrees, about 110 to 250 degrees, about 120 to 240 degrees, about 130 to 230 degrees, about 140 to 220 degrees, about 150 to 210 degrees, about 160 to 200 degrees, about 170 to 190 degrees, etc.

[0077] Similarly, in a further embodiment, the portion to be coated may include angles such as 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 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.

[0078] In an embodiment, the portion to be coated may include a "bent" or curved portion sandwiched between two straight portions of the device. For example, in an embodiment, the straight portions may be connected by the bent or curved portion, and the straight portions may be 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 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. with respect to each other.

[0079] In a further embodiment, the straight portions may include angles with respect to each other of up to 10 degrees, up to 15 degrees, up to 20 degrees, up to 25 degrees, up to 30 degrees, up to 35 degrees, up to 40 degrees, up to 45 degrees, up to 50 degrees, up to 55 degrees, up to 60 degrees, up to 65 degrees, up to 70 degrees, up to 75 degrees, up to 80 degrees, up to 85 degrees, up to 90 degrees, up to 95 degrees, up to 100 degrees, up to 105 degrees, up to 110 degrees, up to 115 degrees, up to 120 degrees, up to 125 degrees, up to 130 degrees, up to 135 degrees, up to 140 degrees, up to 145 degrees, up to 150 degrees, up to 155 degrees, up to 160 degrees, up to 165 degrees, up to 170 degrees, up to 175 degrees, up to 180 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, and the like.

[0080] In a further embodiment, the straight portions may include angles with respect to each other of 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, 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, and the like.

[0081] In a further embodiment, the straight portions can include angles with respect to each other of about 10 to 350 degrees, about 20 to 340 degrees, about 30 to 330 degrees, about 40 to 320 degrees, about 50 to 310 degrees, about 60 to 300 degrees, about 70 to 290 degrees, about 80 to 280 degrees, about 90 to 270 degrees, about 100 to 260 degrees, about 110 to 250 degrees, about 120 to 240 degrees, about 130 to 230 degrees, about 140 to 220 degrees, about 150 to 210 degrees, about 160 to 200 degrees, about 170 to 190 degrees, and the like.

[0082] Similarly, in a further embodiment, the straight portions can include angles with respect to each other 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 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, and the like.

[0083] In an embodiment, after applying a base coat by dip coating or other methods, the catheter is exposed to ultraviolet irradiation 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 in this range can also provide a suitable base coat. In certain embodiments, the ultraviolet irradiation can be applied by a first wavelength between about 200 nm and about 300 nm and a second wavelength between about 300 nm and about 400 nm. In certain embodiments, the wavelengths can include 254 and 365 nm.

[0084] In embodiments, the curing time, or the time the catheter is exposed to ultraviolet irradiation, can range from about 0.5 to about 10 minutes, from about 1 to about 10 minutes, from about 1 to about 8 minutes, from about 0.5 to about 6 minutes, from about 1 to about 6 minutes, from about 1 to about 3 minutes, or from about 0.5 to about 30 minutes. In certain embodiments, the curing time is about 2 minutes.

[0085] In some embodiments, the base coat application process is completed after the curing time is complete.

[0086] (Application of the top coat) In embodiments, a top coat can be applied to the completed base coat. The top coat solution can include a solvent, a top coat polymer, any initiator, and any surfactant. Generally, any solvent or solvent mixture can be utilized so long as the components dissolve in the solvent or solvent mixture. Suitable solvents can include water, alcohols, glycol ethers, aromatics, polar aprotic solvents, and combinations thereof. In some embodiments, the solvent can include methanol, ethanol, isopropyl alcohol, 2-ethoxyethanol, propylene glycol monomethyl ether acetate, benzene, toluene, xylene, dimethylformamide, dimethyl sulfoxide, and combinations thereof.

[0087] In embodiments, the top coat polymer can be dissolved in a selected solvent at a concentration in the range 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 top coat solution. In certain embodiments, the concentration of the top coat polymer is about 25% w / w.

[0088] In embodiments, any initiator can include Norrish type I initiators, Norrish type II initiators, and combinations thereof. Norrish type I initiators or free radical photoinitiators can include benzoin derivatives, methylolbenzoin and 4-benzoyl-1,3-dioxolane derivatives, benzyl ketals, α,α-dialkoxyacetophenones, α-hydroxyalkylphenones, α-aminoalkylphenones, acylphosphine oxides, bisacylphosphine oxides, acylphosphine sulfides, halogenated acetophenone derivatives, and the like.The Norrish type I photoinitiators may include acylphosphine oxides such as Irgacure 2959 (2-hydroxy-4'-(2-hydroxyethoxy)-2-methylpropiophenone), Irgacure 651 (benzyldimethylketal, or 2,2-dimethoxy-1,2-diphenylethanone, Ciba-Geigy), Irgacure 184 (1-hydroxy-cyclohexyl-phenylketone as the active ingredient, Ciba-Geigy), Darocur 1173 (2-hydroxy-2-methyl-1-phenylpropan-1-one as the active ingredient, 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 the active ingredient, Ciba-Geigy), Esacure KIP150 (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 KTO46 (a blend of poly{2-hydroxy-2-methyl-1-[4-(1-methylvinyl)phenyl]propan-1-one}, 2,4,6-trimethylbenzoyldiphenyl-phosphine oxide and a methylbenzophenone derivative, Fratelli Lamberti); 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 can also be used.

[0089] Useable Norrish type I photoinitiators can include benzophenone, xanthone, derivatives of benzophenone (e.g., chlorobenzophenone), blends of benzophenone and benzophenone derivatives (e.g., Photocure 81, a 50 / 50 blend of 4-methylbenzophenone and benzophenone), Michler's ketone, ethyl Michler's ketone, other xanthone derivatives such as thioxanthone and Quantacure ITX (isopropylthioxanthone), benzyl, anthraquinone (e.g., 2-ethylanthraquinone), aromatic ketones such as coumarin, or chemical derivatives or combinations thereof.

[0090] In some embodiments, the formulation of the topcoat can include a combination of Norrish type I and Norrish type II initiators.

[0091] In embodiments, the concentration of the initiator in the solvent can range from about 0.1% to about 6% w / w. In some embodiments, the concentration of the initiator in the solvent can be about 0.5 w / w.

[0092] In embodiments, the topcoat solution can also include a surfactant. Generally, any surfactant may be used. In some embodiments, the surfactant can include sodium lauryl sulfate, Tween 20, Span 80, Triton X-100, Pluronic F68, Pluronic L-81, combinations thereof, and derivatives thereof. Any surfactant can be dissolved in the selected solvent at a concentration in the range 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.

[0093] In some embodiments, to apply a topcoat to a base-coated catheter, the length of the catheter to be coated is placed in the basecoat solution. In embodiments, the "soaking" time, or the time the catheter is soaked in the basecoat solution, ranges from about 0.2 to about 20 minutes, about 0.5 to about 20 minutes, about 2 to about 15 minutes, about 3 to about 15 minutes, or about 8 to about 12 minutes. In some embodiments, the soaking time can be about 10 minutes.

[0094] In another embodiment, the topcoat can be applied by spraying, brushing, spin coating, etc., or combinations thereof, with or without dip coating.

[0095] In some embodiments, only a portion of the catheter is coated with the topcoat. In that case, a portion of the catheter can be masked so that the topcoat is not applied to the masked area.

[0096] In embodiments, after applying the topcoat by dip coating or other methods, the catheter is exposed to ultraviolet light at wavelengths 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 in this range can also provide a suitable basecoat. In certain embodiments, the ultraviolet light can be applied by a first wavelength between about 200 nm and about 300 nm and a second wavelength between about 300 nm and about 400 nm. In certain embodiments, the wavelengths can include 254 and 365 nm.

[0097] The curing time of the topcoat, or the time the catheter is exposed to ultraviolet irradiation, ranges from about 0.5 to about 4 minutes, about 1 to about 4 minutes, about 1 to about 3 minutes, about 0.5 to about 3 minutes, about 1 to about 5 minutes, about 0.5 to about 3 minutes, or about 0.5 to about 50 minutes. In certain embodiments, the curing time is about 2 minutes.

[0098] The coatings described herein can reduce the maximum dynamic friction force [gf] when compared to uncoated devices. In some embodiments, the coating can reduce the maximum dynamic friction force by approximately, for example, 10%, 20%, 30%, 40%, 50%, 60%, or even lower. In another embodiment, the coating can reduce the maximum dynamic friction force by about 75%.

[0099] The coatings described herein can reduce the average dynamic friction force [gf] at 100 cycles at a displacement of 60 mm when compared to uncoated devices. In some embodiments, the coating can reduce the maximum dynamic friction force by approximately, for example, 10%, 20%, 30%, 40%, 50%, 60%, or even lower. In another embodiment, the coating can reduce the maximum dynamic friction force by about 75%.

[0100] The coatings described herein can enhance lubricity when compared to uncoated devices. In some embodiments, the coating can enhance lubricity by approximately, for example, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, etc.

[0101] In some embodiments, the coating can enhance lubricity by approximately, for example, 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.

[0102] The coatings described herein are applied to an inner support catheter. In some embodiments, the inner support catheter may be partially coated. In another embodiment, the inner support catheter may be fully coated. In some embodiments, a part or portion of the inner support catheter is coated. The coated portion may be the spherical portion of the inner support catheter. In another embodiment, the coated portion may be the non-spherical portion of the inner support catheter. In another embodiment, the specific portion where friction is observed is coated. In some embodiments, the length of the specific portion may vary according to the amount of friction confirmed.

[0103] In some embodiments, the coating is not applied to the distal portion of the catheter. For example, other devices may have a coating applied over the entire distal portion of the catheter to help reduce friction. However, applying a coating to the distal portion of the inner support catheter causes the inner support catheter to lose its position when advancing a guidewire through the lumen or advancing a guide catheter over the inner support catheter. A coating applied to the distal end of the inner support catheter may help reduce friction but also reduces stability. Therefore, the coatings described herein applied to specific portions of the inner support catheter can reduce friction without reducing stability.

[0104] The coatings described herein may be applied to specific portions of the catheter. In some embodiments, the specific portion may be the specific portion where friction is observed. In another embodiment, the specific portion may be the proximal end of the catheter. In some embodiments, the specific portion may be a constricted, angled, or spherical region / portion of the catheter.

[0105] In some embodiments, methods for applying a coating to a particular portion of a catheter are described, including a base coat comprising a copolymer of a first tetrahydrofurfuryl acrylate monomer and a second monomer comprising a functional group capable of further derivatization and a plurality of reactive moieties, and a top coat comprising a hydrophilic polymer having more than two reactive moieties per molecule. In another embodiment, methods for applying a coating to a spherical portion of an inner support catheter are described, including a base coat comprising a copolymer of a first tetrahydrofurfuryl acrylate monomer and a second monomer comprising a functional group capable of further derivatization and a plurality of reactive moieties, and a top coat comprising a hydrophilic polymer having more than two reactive moieties per molecule.

[0106] (Example 1) (Preparation of Base Coat Copolymer) Add 80.0 g of tetrahydrofurfuryl acrylate, 18.5 g of hydroxybutyl acrylate, and 250 mL of toluene to a 1 L round bottom flask. Purge the solution with argon gas for 30 minutes to degas. Then add 1.0 gram of AIBN initiator and purge the mixture with argon for an additional 10 minutes. Immerse the flask in an oil bath at 80 °C and attach a reflux condenser with an argon inlet. Heat the mixture under argon for 16 hours. Cool the reaction product, precipitate it with 12 L of cold MTBE, recover the precipitate - viscous polymer, and dry it in vacuo. Typical yields are 85 - 95%.

[0107] Dissolve the dried polymer in anhydrous DMF (200 mL, about 0.5 g / mL) and treat it with 0.84 mL of triethylamine and 3.0 mL of isocyanatoethyl acrylate. Heat the mixture at 45 °C for 5 hours. Precipitate the polymer with 1.2 L of cold MTBE, wash it with 2 × 200 ml of MTBE, and dry it under high vacuum.

[0108] (Example 2) (Preparation of Liquid Base Coat Solution) Dissolve 6.75 g of the polymer of Example 1 in 45.0 mL of propylene glycol monomethyl ether acetate in a suitable container. Then, add 0.34 g of Pluronic L-81 surfactant, 135 mg of benzophenone, and 135 mg of 1-hydroxycyclohexyl phenyl ketone. Shake for 30 minutes until completely dissolved to obtain a clear and homogeneous solution.

[0109] (Example 3) (Coating of the microcatheter with the basecoat solution) First, insert a tightly fitting stainless-steel mandrel inside the hollow lumen, and then prepare a 12-inch length (outer diameter 0.027”) portion of the microcatheter with an outer surface composed of Grilamid L25 for coating by wiping the outer surface with acetone. Then, plasma-treat the microcatheter portion with argon plasma (365 sccm, 300 watts, 500 mtorr), followed by oxygen plasma (120 sccm, 150 watts, 400 mtorr). Transfer the liquid basecoat formulation prepared in Example 2 to a glass tube (12” in length, 0.22” in inner diameter) stoppered at the bottom. Then, place the microcatheter portion into the coating solution in the glass tube and let it stand for 5 minutes. Take out the microcatheter portion and immediately cure it by UV irradiation (254 nm λ, 1.3 J / cm2 UV dose) for 2 minutes to polymerize the basecoat onto the Grilamid substrate.

[0110] (Example 4) (Preparation of the topcoat macromer) Dry 50 grams of PEG (Mw 4,000) by azeotropic distillation with toluene. Treat the solution of PEG in 250 mL of toluene with 30 mL of dichloromethane, followed by the addition of 7.0 mL of triethylamine and 4.04 mL of acryloyl chloride. Stir the reaction mixture for 5 hours, then filter the precipitated salt, and isolate the topcoat macromer by precipitation from 1 L of cold MTBE. Separate the solid by filtration, wash it further with 200 mL of MTBE, and dry it under high vacuum overnight.

[0111] (Example 5) (Preparation of Topcoat Solution) In a container, 9.0 g of polyethylene glycol diacrylate (4,000 Mw) adjusted in Example 4 is shaken and dissolved in 45.0 mL of methanol. Then, 0.23 g of Pluronic L-81 surfactant, 90 mg of benzophenone, and 90 mg of 1-hydroxycyclohexyl phenyl ketone are added. Heating at 55 °C for 2 minutes results in complete dissolution, yielding a transparent and homogeneous solution.

[0112] (Example 6) (Coating of Microcatheter with Topcoat Solution) The topcoat solution prepared in Example 5 is transferred to a glass tube with a stopper at the bottom, and the microcatheter portion coated with the basecoat in Example 3 is placed into the glass tube and left in the topcoat solution for 10 minutes. Then, the microcatheter portion is taken out and immediately cured by UV irradiation (254 nm λ, 1.3 J / cm2 UV dose) for 2 minutes to polymerize the topcoat on the basecoat.

[0113] (Example 7) (Lubricity) The microcatheter samples prepared in Example 6 were tested using an Instron 5943 material testing machine with a 5N static load cell to evaluate lubricity. A mechanical clamp fixture was attached to the load cell, and the upper length of the microcatheter sample was pulled through a hydraulic clamp fixture (clamping force 1 pound) immersed in a heated (37°C) water bath containing distilled water, and the upper part was held. The test method was to repeatedly pull each sample 20 cycles up to 100 mm at a pulling speed of 254 mm / min. One cycle was measured starting from a displacement of 0 mm with the hydraulic clamp closed on the sample. Then, the sample was pulled through the hydraulic clamp, displaced 100 mm, and finally the hydraulic clamp was opened to return the sample to a displacement of 0 mm. The maximum dynamic friction force and the average dynamic friction force at a displacement of 60 mm were measured and shown in the following table. The table includes, for comparison, the lubricity measurement results for 20 cycles of uncoated samples.

[0114]

Table 1

[0115] The coating of Example 6 shows an improvement in lubricity compared to the uncoated samples.

[0116] (Disclosed embodiments) Embodiment 1) A method for reducing the maximum dynamic friction force [gf] of a medical device, applying a base coat to the device, applying a top coat to the base coat, comprising the base coat and the top coat form a lubricious surface on the medical device, thereby reducing the maximum dynamic friction force. Method.

[0117] Embodiment 2) The method according to Embodiment 1, wherein the base coat and the top coat are applied to at least 1% of the surface area of the device.

[0118] Embodiment 3) The method according to Embodiment 2, wherein the base coat and the top coat are applied to at least 5% of the surface area of the device.

[0119] Embodiment 4) The method according to Embodiment 3, wherein the base coat and the top coat are applied to at least 10% of the surface area of the device.

[0120] Embodiment 5) The method according to Embodiment 2, wherein the base coat comprises a copolymer of a first tetrahydrofurfuryl acrylate monomer and a second monomer.

[0121] Embodiment 6) The method according to Embodiment 5, wherein the second monomer comprises a hydroxyl, amine, or carboxylic acid group.

[0122] Embodiment 7) The method according to Embodiment 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-aminoethyl methacrylamide, acrylic acid, methacrylic acid, β-carboxyethyl acrylate, combinations thereof, or derivatives thereof.

[0123] Embodiment 8) The top coat is the method according to Embodiment 1, comprising 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).

[0124] Embodiment 9) The base coat is the method according to Embodiment 1, which is applied to the angled, constricted, or spherical portion of the medical device.

[0125] Embodiment 10) The base coat is made by dissolving the copolymer, and the monomer in the solvent is selected from benzene, toluene, xylene, dimethylformamide, dimethyl sulfoxide, dioxane, 2-methyltetrahydrofuran, anisole, benzonitrile, chlorinated aromatic solvents, diisopropyl ether, diglyme, butanol, and combinations thereof, which is the method according to Embodiment 5.

[0126] Embodiment 11) A medical device comprising an angled, bent, or constricted region, wherein the angled, bent, or constricted region comprises a lubricating coating.

[0127] Embodiment 12) The medical device according to Embodiment 11, wherein the angled, bent, or constricted region is sandwiched between straight regions.

[0128] Embodiment 13) The straight region is a medical device according to Embodiment 12 that forms an angle of at least 10 degrees with respect to each other.

[0129] Embodiment 14) The device is a medical device according to Embodiment 13 that includes a catheter.

[0130] Embodiment 15) The straight region is a medical device according to Embodiment 14 that includes an angle of at least 15 degrees.

[0131] Embodiment 16) The straight region is a medical device according to Embodiment 15 that includes an angle of at least 20 degrees.

[0132] Embodiment 17) The lubricating coating is a medical device according to Embodiment 11 that includes a base coat.

[0133] Embodiment 18) The lubricating coating is a medical device according to Embodiment 17 that includes a top coat.

[0134] Embodiment 19) The lubricating coating is a medical device according to Embodiment 18 that reduces the maximum dynamic frictional force [gf] of the device by 10% compared to a device without the coating.

[0135] Embodiment 20) The lubricating coating is a medical device according to Embodiment 18 that reduces the maximum dynamic frictional force [gf] of the device by 20% compared to a device without the coating.

[0136] Embodiment 21) The base coat is a medical device according to Embodiment 17 that includes a copolymer of a first tetrahydrofurfuryl acrylate monomer and a second monomer containing a hydroxyl, amine, or carboxylic acid group.

[0137] Embodiment 22) The top coat is the medical device according to Embodiment 18, comprising 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).

[0138] Preferred embodiments are described in this specification and the accompanying drawings, but it will be understood by those skilled in the art that many variations and modifications are possible. Therefore, the scope of the present invention should not be limited by the specific embodiments and examples described herein, but should be considered to include alternative embodiments and equivalents.

[0139] Unless otherwise specified, all numbers representing amounts such as component amounts, molecular weights, reaction conditions, etc. used in the specification and claims should be understood to be modified by the term "about" in all instances. Therefore, unless indicated to the contrary, the numerical parameters shown in this specification and the appended claims are approximate values that may vary depending on the desired characteristics to be obtained by the present invention. At a minimum, and not as an attempt to limit the application of equivalents to the claims, each numerical parameter should be construed at least in light of the number of significant figures reported and by applying ordinary rounding means. Although the numerical ranges and parameters indicating the broad scope of the present invention are approximate, the numerical values shown in the specific examples are reported as accurately as possible. However, any numerical value inherently includes errors that necessarily result from the standard deviation found in each test measurement.

[0140] The terms "a", "an", "the", and similar references used in the context of describing the present invention (especially in the context of the following claims) should be construed to cover both the singular and plural forms unless otherwise stated or clearly contradicted by the context. The recitation of a range of values herein is merely intended to serve as a shorthand for referring individually to each separate value within the range. Unless otherwise stated herein, each separate value is incorporated herein as if it were individually recited herein. All methods described herein can be performed in any suitable order unless otherwise stated herein or clearly contradicted by the context. The use of any and all examples, or exemplary language (e.g., "such as") provided herein is intended to better clarify the invention and is not intended to limit the scope of the invention as claimed. The description herein should not be construed as indicating any element other than those claimed as essential to the practice of the invention.

[0141] The grouping of alternative elements or embodiments of the invention disclosed herein should not be construed as a limitation. The components of each group can be referred to and claimed individually or in any combination with other components of the group or other elements found herein. For reasons of convenience or patentability, it is anticipated that one or more components of a group may be included in or deleted from the group. In the event of such inclusion or deletion, the specification is considered to include the modified group and meets all recitations of the Markush groups used in the appended claims.

[0142] This specification describes some embodiments of the present invention, including the best mode contemplated by the inventors for carrying out the present invention. Of course, variations of these described embodiments will be apparent to those skilled in the art upon reading the foregoing description. The inventors expect those skilled in the art to appropriately use such variations, and the inventors intend for the present invention to be practiced in ways other than those specifically described herein. Accordingly, the present invention includes all changes and equivalents of the subject matter recited in the appended claims as permitted by applicable law. Further, any combination of the above-described elements in all possible variations thereof is included in the present invention unless otherwise stated herein or otherwise clearly contradicted by context.

[0143] Further, throughout this specification, numerous patents and printed publications are referenced. Each of the above-cited patents and printed publications is hereby incorporated by reference in its entirety.

[0144] 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. Accordingly, as an example and not a limitation, alternative configurations of the present invention may be utilized in accordance with the teachings of this specification. Accordingly, the present invention is not precisely limited as shown and described.

Claims

Claim 1 A method for reducing the maximum dynamic frictional force [gf] of a medical device, comprising: applying a base coat to the device; applying a top coat to the base coat; wherein the base coat and the top coat form a lubricating surface on the medical device, thereby reducing the maximum dynamic frictional force. A method. Claim 2 The method according to claim 1, wherein the base coat and the top coat are applied to at least 1% of the surface area of the device. Claim 3 The method according to claim 2, wherein the base coat and the top coat are applied to at least 5% of the surface area of the device. Claim 4 The method according to claim 3, wherein the base coat and the top coat are applied to at least 10% of the surface area of the device. Claim 5 The method according to claim 2, wherein the base coat comprises a copolymer of a first tetrahydrofurfuryl acrylate monomer and a second monomer. Claim 6 The method according to claim 5, wherein the second monomer comprises a hydroxyl, amine, or carboxylic acid group. Claim 7 The method according to 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-aminoethyl methacrylamide, acrylic acid, methacrylic acid, β-carboxyethyl acrylate, combinations thereof, or derivatives thereof. Claim 8 The method according to claim 1, wherein the top coat comprises a 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). ​

9. The method according to claim 1, wherein the base coat is applied to the angled, tapered, or spherical portions of the medical device.

10. The method according to claim 5, wherein the base coat is made by dissolving the copolymer, and the monomers in the solvent are selected from 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 angled, bent, or tapered regions, wherein the angled, bent, or tapered regions comprise a lubricating coating.

12. The medical device according to claim 11, wherein the angled, bent, or tapered regions are sandwiched between straight regions.

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

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

15. The medical device according to claim 14, wherein the straight regions comprise an angle of at least 15 degrees.

16. The medical device according to claim 15, wherein the straight regions comprise an angle of at least 20 degrees.

17. The medical device according to claim 11, wherein the lubricating coating comprises a base coat.

18. The medical device according to claim 17, wherein the lubricating coating comprises a top coat.

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

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

21. The medical device according to claim 17, wherein the base coat comprises a copolymer of a first tetrahydrofuryl acrylate monomer and a second monomer containing a hydroxyl, amine, or carboxylic acid group.

22. The top coat of the medical device according to claim 18 contains 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).

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