JP5688791B2 - Surface modification for coating - Google Patents

Description

  The present invention relates generally to biocompatible coatings. More particularly, the present invention relates to medical device surface modifications suitable for applying biocompatible coatings.

  Implantable medical devices such as pacemakers, defibrillators, nerve stimulators, venous inserters and catheters are well known devices that help improve health and maintain life. However, despite the significant advantages provided by implantable medical devices, their use can create serious medical problems that can lead to blood clots, ie death. A thrombus is a clot formation within a blood vessel that inhibits blood flow, which can lead to cerebral infarction, heart attack, organ failure, and death.

  A thrombus associated with a medical device initially results from the interaction between the blood and the surface of the medical device when they come into contact with each other. As soon as the blood contacts the medical device, platelets and other blood components clot at the surface of the medical device and begin to form clots. Blood clotting is known to occur on metallic and polymeric materials, which are substances used to manufacture medical devices.

  After blood clotting has occurred on the surface of the medical device, the mass can detach from the surface of the device and move in the bloodstream and can remain in the blood vessel and impede blood flow. Thrombus is a particularly serious problem for permanently implanted devices that are in continuous contact with blood.

  Much work has been done to develop coatings that reduce cell attachment and activation. These coatings are called biomimetic coatings, but can prevent the formation of blood clots and reduce the likelihood of thrombosis.

  One group of such biomimetic coatings include surfactants described in US Pat. Nos. 6,759,388, 7,276,474, and US Patent Application Publication Nos. 20080244798 and 20080262614 to Marcan et al. These documents are cited as reference materials in the present application.

  These coatings provide good clot suppression. However, adhesion of these coatings to many medical device surfaces, especially those that are in constant contact with blood, can benefit from improved coating adhesion. In particular, adhesion to polymer surfaces consisting of silicone, polyurethane and polyether block amide (PEBA) materials is not ideal.

US Pat. No. 6,759,388 US Pat. No. 7,276,474 US Patent Application Publication No. 20080244798 US Patent Application Publication No. 20080262614

  Accordingly, it is an object of the present invention to provide a means for modifying the surface of a medical device and improving the adhesion of a biomimetic polymer coating to various medical device surfaces.

  The present invention resides in modifying material substrates used in implantable medical devices to improve adhesion of biomimetic surfactant coatings. Biomimetic surfactants, which are described in more detail below, are designed to reduce protein, platelet and leukocyte adhesion, and consequently reduce the likelihood of thrombosis.

  Biomimetic surfactant coatings developed by Malkan et al. Are known to reduce platelet adhesion and activation on the coating surface. The adhesion of this coating to the substrate surface is controlled primarily by the hydrophobic interaction between the surfactant and the substrate surface. Adhesive strength varies depending on the chemical composition of the substrate. The adhesive strength is proportional to the hydrophobicity of the substrate surface. The higher the hydrophobicity of the substrate surface, the stronger the bond strength between the substrate surface and the surfactant coating.

  Common medical device substrates are made of silicone, polyurethane and polyether block amides. The last substance is manufactured under the trade name “Pebax”. These polymeric materials are often used in the manufacture of a wide range of medical devices such as, for example, catheters, venous inserters, pacemakers, defibrillators, neurostimulators and associated lead wires.

  Therefore, it is desirable to modify the surface to further improve the adhesion of the biomimetic surfactant by increasing the hydrophobicity of these materials.

  The present invention does exactly this. In the present invention, the surface of a substrate is modified by two methods to change its hydrophobicity. The first method modifies the substrate surface by providing a “tie layer” with increased hydrophobicity. This “tie layer” is placed on the substrate surface to form a composite bond between the substrate surface and the biomimetic coating. This “tie layer” acts as an intermediate layer that improves the binding of the biomimetic surfactant coating to the medical device surface. In the second method, the surface of the substrate is modified by incorporating an additive (dopant) having increased hydrophobicity, and this additive is added in the manufacturing process of the substrate material. Such incorporation of additives results in a substrate surface with increased hydrophobicity.

  Here, the term “hydrophobic” is defined as the property of repelling water and not binding to water or being insoluble in water. The term “biomimetic” is defined as the property of mimicking the interaction of living cells at the molecular level without causing adverse effects or reactions in the body. The term “non-thrombogenic” is defined as the property of preventing blood clotting in blood vessels. The term “substrate” is defined as a base material that can be modified by applying a coating on the surface of the source material or by incorporating an additive material during the manufacturing process. In the present invention, the substrate surface is the surface of a medical device.

  When the polymer surface is fully modified, a biomimetic surfactant polymer such as poly (N-vinyldextran aldonamide-co-N-vinylhexanamide), or a derivative thereof, can be modified with hydrophobically modified groups It is given on the material surface.

  Biomimetic surfactants include a polymer backbone of repeating monomer units with functional groups for bonding with side chains. This surfactant contains two main functional groups: a hydrophobic side chain functional group and a hydrophilic side chain functional group. The hydrophobic side chain functional group affects the bond adhesion of the surfactant to the substrate surface. Hydrophilic side-chain functional groups control the biomimetic properties of the surfactant and form an effective non-thrombogenic surface that delays blood clotting.

  A polymer tie layer consisting of parylene, a silicone polycarbonate copolymer, a polyurethane polycarbonate copolymer, or an unsaturated long chain carboxylic acid amide, such as erucamide, is first provided on the substrate surface of the medical device. After this hydrophobic polymer layer is provided, a biomimetic surfactant is provided on the initial hydrophobic polymer layer. The first hydrophobic polymer layer acts as an intermediate or tie layer that bonds the biomimetic coating to the material on the device surface.

  Thus, a medical device surface modified by using an intermediate tie layer has sufficient hydrophobicity to form a secure adhesive bond with the biomimetic surfactant.

  The hydrophobicity of the substrate surface can also be increased by adding an unsaturated long chain carboxylic acid amide, such as erucic acid amide, as an additive. During production, a small amount of unsaturated long-chain carboxylic acid amide is mixed into a polymer such as polyurethane to form a polyurethane substrate having a surface with increased hydrophobicity. This polymer surface therefore has a hydrophobic surface sufficient to form a reliable adhesive bond of the biomimetic surfactant.

It is a figure which shows the chemical structure of the biomimetic surfactant used in this invention. It is sectional drawing which shows the connection layer pinched | interposed between the base-material surface and biomimetic coating. It is sectional drawing which shows the method of measuring a contact angle.

  In the present invention, to reduce the occurrence of thrombosis, the surface of the medical device improves the adhesion of poly (N-vinyldextran aldonamide-co-N-vinylhexanamide), a preferred biomimetic surfactant. Is modified as follows. As shown in FIG. 1, the biomimetic surfactant is composed of a chemical structure 10 composed of a bond between a hydrophobic molecular chain and a hydrophilic molecular chain. This hydrophobic molecular chain is composed of a poly (N-vinylhexanoyloxy) (PNVH) component 12, and the hydrophilic molecular chain is composed of a poly (N-vinyldextran aldonamide) (PNVDA) component 14. The molecular weight of this desirable surfactant is from about 1,000 to about 2,000,000 daltons.

  The biomimetic surfactant is provided on the substrate surface by coating. Preferred polymeric substrate materials include silicone, polyurethane and polyether block amides known by the trade name “Pebax”. It is believed that the surfaces of medical devices such as pacemakers, defibrillators, nerve stimulators, inserters, leads, catheters and stents can be modified.

  Other biomimetic surfactants such as poly (N-vinyl dextran aldonamide-co-N-vinyl dodecanoamide) (PNVDA-co-PNVL), poly (N-vinylhexylamine-co-N-vinyl) Heparinamine) (PNVHA-co-PNVHep A), poly (N-vinylhexylamine-co-N-vinylheparinamine-co-N-vinylmaltonamide) (PNVHA-co-PN-VHepA-co-PNVM), And poly (N-vinyl-5-peptidyl-pentylamine-co-N-vinyldextran aldoneamine-co-N-vinylhexylamine) (PVAm (Pep: Dex: Hex)) can also be used.

  As shown in FIG. 1, preferred biomimetic surfactants are poly (N-vinylhexanoamide) (PNVH) 12 which is a large number of hydrophobic side chains and poly (N--) which is a large number of hydrophilic side chains. It has a comb-like structure consisting of a flexible polymer backbone 16 linked to a conjugate of vinyl dextran aldonamide) (PNVDA) 14.

  This hydrophobic side chain 12 consists of an alkyl group linked to the polymer backbone 16 via an ester bond, an amine bond or an amide bond. Preferably, the hydrophobic side chain 12 is attached to the polymer backbone 16 by reacting alkanoyl (CH3 (-CH2-) nCO-) or alkanal (CH3 (CH2-) nCHO) with the backbone homopolymer. .

  In the present invention, the alkyl chain of the biomimetic surfactant molecule is hydrophobic, and associates with a hydrophobic substance (linking layer or additive) on the surface of the substrate via a hydrophobic interaction. The aqueous environment of the surfactant drives the hydrophobic alkyl chain of the surfactant toward the hydrophobic material of the substrate. Such hydrophobic-hydrophobic association results in a bond between the biomimetic coating and the hydrophobic material of the substrate.

  As mentioned earlier, the hydrophilic side chain controls the biomimetic properties of the surfactant. In order to form a coating that prevents adhesion of non-specific plasma proteins to the substrate surface, the surfactant polymer is preferably composed of a number of hydrophilic side chains made from oligosaccharides having an average molecular weight of 7000 Daltons or less. Become. Such surfactant polymers are ionic or non-ionic and are not limited to natural oligosaccharides such as dextran. The hydrophilic side chains are attached to the polymer backbone 16 via ester bonds, secondary amine bonds, or preferably amide bonds.

  Alternatively, charged oligosaccharides, preferably negatively charged oligosaccharides having an average molecular weight of 10,000 daltons or less, and oligopeptides comprising from about 3 to about 30 amino acid residues are preferred. The amino acid sequence of the oligopeptide interacts with protein receptors on the cell surface such as endothelial cells.

  The substrate surface can be modified by either of two preferred methods. The first preferred method utilizes the application of a coating that is a tie layer, whereby a polymer layer having increased hydrophobicity is first provided on the substrate surface. This polymer tie layer is provided directly on the rough surface of the substrate and acts as an intermediate layer that facilitates bonding between the substrate, ie the surface of the medical device and the biomimetic surfactant coating.

  In a second preferred method, a hydrophobic modifier is doped into the substrate material and incorporated into the polymer material of the substrate during the formation of the substrate. As a result of such a method, it becomes a base material having an increased surface hydrophilicity and can form a strong adhesive bond with the biomimetic surfactant. Unlike the coating method, this additive modification method does not require the use of a tie layer to ensure a non-thrombogenic coating on the substrate surface.

  In a preferred tie layer method, a thin layer of hydrophobic polymer material is first applied to a clean substrate surface rough. Preferred hydrophobic polymer materials include parylene, silicone polycarbonate copolymers, polyurethane polycarbonate copolymers, and unsaturated long chain carboxylic acid amides such as erucic acid amides. One or multiple thin layers of the hydrophobic tie layer material are sandwiched between the substrate material and the biomimetic coating material. FIG. 2 shows a specific example of the base material surface modified by providing a connecting layer. As shown in this figure, the composite 20 is such that the top surface of the substrate 22 is bonded to the bottom surface of the hydrophobic linking layer 24 and the bottom surface of the biomimetic surfactant coating 26 is bonded to the top surface of the linking layer 24. It is formed.

  In a first preferred embodiment, parylene is provided by vapor deposition. A layer of about 2.5 nanometers of parylene is provided directly on the clean rough surface of the substrate. It is also possible to provide a plurality of layers with a thickness in the range of about 1 to 3000 nanometers.

  In a second preferred tie layer coating method, a layer of an unsaturated long chain carboxylic amide such as erucamide is provided on the substrate surface. First, a tie layer solution consisting of erucamide and tetrahydrofuran (THF) solution is prepared by dissolving erucamide in THF. Preferably, erucic acid amide in an amount of 0.1 to 10 weight percent is added to the tetrahydrofuran solvent.

  A tie layer having a preferred thickness of 0.1 to 10 micrometers is applied to the clean substrate surface by either spray coating, brush coating, or dip coating. A plurality of layers having a thickness of 0.1 to 10 micrometers can also be provided on the substrate surface. After the solvent mixture is applied to the substrate surface, it is allowed to dry as it is before the biomimetic surfactant coating is applied.

  In a third preferred tie layer method, a silicone polycarbonate copolymer is applied to the substrate surface. Preferably, about 0.1 to about 10 weight percent of the silicone polycarbonate copolymer is dissolved in a tetrahydrofuran (THF) solvent. Alternatively, dimethylacetamide, hexane or toluene can be used to dissolve the silicone polycarbonate material. Preferably, a coating solution of silicone polycarbonate copolymer in the range of about 0.1 to 10 weight percent in hexane is prepared.

  In a third example, a layer of about 100 nanometers thickness is provided on a rough surface of a clean substrate surface. Multiple layers having a thickness of about 1 to about 10 micrometers can also be provided. After the solvent mixture is applied to the substrate surface, it is dried in ambient air before applying the biomimetic surfactant coating.

  In a fourth preferred tie layer method, a polyurethane polycarbonate copolymer, such as the “Bionate” family of polyurene polycarbonate copolymers produced by DSM-PTG, is applied to the substrate surface. The polyurethane polycarbonate copolymer is dissolved in a range of about 0.1 to 10 weight percent polyurethane polycarbonate copolymer in tetrahydrofuran (THF). Alternatively, dimethylacetamide (DMAC) can be used to dissolve the polyurethane polycarbonate copolymer material.

  In a fourth example, a layer about 100 nanometers thick is provided on the clean substrate surface. Multiple layers having a thickness of about 1 to about 10 micrometers can also be provided. After the above solvent mixture is applied to the substrate surface, it is dried in ambient air before the biomimetic surfactant coating is applied.

  In addition to the solution method described above, the hydrophobic tie layer can also be applied to the substrate using any of the following other methods, including powder coating, melt extrusion, Langmuir-Brown. Examples include the jet method (Langmuir-Blodgett process), gas plasma deposition method, chemical vapor deposition method, physical vapor deposition method, spray coating, dip coating, or spin coating.

  It is preferable to prepare a hydrophobic linking layer solution by dissolving the hydrophobic component in tetrahydrofuran THF, but other solvents such as ethanol, methanol, ethyl acetate, dimethylformamide (DMF), dimethylacetamide (DMAC), dimethyl The linking layer solution can also be prepared by dissolving the hydrophobic component using sulfoxide (DMSO), dioxane, N-methylpyrrolidone, chloroform, hexane, heptane, cyclohexane, toluene, formic acid, acetic acid, and / or dichloromethane.

  Single or multiple coatings of the tie layer solution can be applied to the substrate surface to obtain the desired thickness. Examples of the base material include, but are not limited to, biocompatible metals and polymers. Polyurethane, silicone, polyethylene, polypropylene, polyether block amide, polyester, polyether ether ketone, titanium, titanium alloy Stainless steel, gold, platinum, palladium, MP35N can also be used.

  Alternatively, the surface of the substrate can be modified by adding a hydrophobic additive. This additive may be a small amount of a hydrophobic component added during manufacture of the substrate material. After the polymeric material containing the additive has been extruded into a final shape, it is ready to be coated with a biomimetic surfactant polymer. Erucamide is one of the preferred additives.

  In a first embodiment of the method using additives, about 1 weight percent erucamide is first dissolved in tetrahydrofuran (THF), toluene or other compatible organic solvent. This solvent mixture is then mixed with the base polymer before extrusion. Although about 1 weight percent erucamide is preferred, erucamide in the range of about 0.1 to 10 weight percent can be dissolved in an organic solvent to make an additive mixture.

  Thereafter, about 1 to 30 weight percent of the additive mixture is incorporated into the base polymer. This solvent mixture is mixed into the base polymer and dried before it is extruded into a final shape. The base polymer into which the additive can be mixed is a biocompatible polymer, but is not limited, and examples thereof include polyurethane, polyester, polyether ether ketone, and preferably polyurethane and polycarbonate.

  After the substrate surface has been modified by providing a hydrophobic tie layer or by adding a hydrophobic additive, a biomimetic coating such as poly (N-vinyldextran aldonamide-co-N-vinylhexanamide) It is applied to the modified substrate surface. However, prior to applying the biomimetic coating to the modified surface, the hydrophobicity of the substrate surface exhibits the property of ensuring adhesion of a suitable surfactant coating. In order to determine the hydrophobicity of the substrate surface that guarantees sufficient surfactant adhesion, a sessile drop method is preferred which measures the contact angle of the droplet to the substrate surface.

  In the cecil dropping method, one drop of liquid is placed on the substrate surface, and the contact angle is measured. Here, the contact angle is defined as an angle at which the liquid contacts the surface of the solid substrate at the air interface, as shown in FIG.

  To characterize the hydrophobicity of the modified substrate surface, a drop of water is placed on the modified substrate surface and its contact angle is measured using the cecil dropping method. A satisfactory hydrophobic surface has a contact angle of 40 degrees or more.

  Once the substrate surface is fully modified, a solution of the biomimetic coating is prepared. In a preferred embodiment, an aqueous solution of poly (N-vinyldextran aldonamide-co-N-vinylhexanamide) in the range of about 1 to about 25 weight percent is prepared. Alternatively, the aqueous surfactant solution can be mixed with isopropyl alcohol. When using isopropyl alcohol, a solvent solution of about 45 to about 55 weight percent isopropyl alcohol is added to the aqueous surfactant solution.

  Once the surfactant and solvent mixture is made, the mixture is applied to the substrate surface and allowed to dry in ambient air. This surfactant solution is preferably applied by dip coating. This hydrophobically modified substrate surface binds to the hydrophobic side chains of the non-thrombogenic coating material to ensure proper adhesion.

  Other means such as spray coating, spin coating or brush coating can also be used to provide a biomimetic coating on the modified substrate surface.

  Thus, the present invention teaches various formulations and methods for incorporating biomimetic surfactants into medical device substrates. The polymer substrate thus modified has improved blood compatibility on the surface, including the ability to prevent clot formation. This makes the polymer material a preferred material candidate for use in the manufacture of implantable medical devices.

DESCRIPTION OF SYMBOLS 10 Chemical structure which consists of a coupling | bonding of a hydrophobic molecular chain and a hydrophilic molecular chain 12 Hydrophobic side chain 14 Hydrophilic side chain 16 Polymer backbone 20 Composite 22 Base material 24 Hydrophobic connection layer 26 Biomimetic surfactant coating

Claims (26)

a) a hydrophobic substrate surface;
b) a hydrophobic tie layer comprising an unsaturated carboxylic acid amide;
c) a substrate containing a biomimetic surfactant, wherein the unsaturated carboxylic acid amide linking layer is located between the hydrophobic substrate surface and the biomimetic surfactant. And,
d) The unsaturated carboxylic acid amide linking layer is hydrophobically bonded to the surface of the hydrophobic substrate along the bottom surface of the linking layer, and the unsaturated carboxylic acid amide is along the top surface of the linking layer. A base material characterized in that it is hydrophobically bound to the biomimetic surfactant . The alkyl chain of the biomimetic surfactant is hydrophobically associated with the unsaturated carboxylic acid amide in the hydrophobic linking layer to form a hydrophobic bond therebetween. The base material as described in. The substrate according to claim 1, wherein the hydrophobic linking layer contains erucic acid amide . The biomimetic surfactant is poly (N-vinyldextran aldonamide-co-N-vinylhexanamide), poly (N-vinyldextran aldonamide-co-N-vinyldodecanoamide) (PNVDA-co-PNVL) ), Poly (N-vinylhexylamine-co-N-vinylheparinamine) (PNVHA-co-PNVHep A), poly (N-vinylhexylamine-co-N-vinylheparinamine-co-N-vinylmaltononamide) ) (PNVHA-co-PN-VHepA-co-PNVM), and poly (N-vinyl-5-peptidyl-pentylamine-co-N-vinyldextranaldoneamine-co-N-vinylhexylamine) (PVAm (Pep The substrate according to claim 1, wherein the substrate is selected from the group consisting of: Dex: Hex)) . The base material is selected from the group consisting of silicone, polyurethane, polyether block amide (PEBA), stainless steel, titanium, gold, platinum, palladium, silver, polycarbonate and polyurethane. Base material. The said substrate surface is a surface selected from the group of medical devices consisting of pacemakers, defibrillators, neurostimulators, inserters, leads, catheters and stents . Base material. The substrate according to claim 1, wherein the hydrophobic linking layer has a thickness of 0.1 to 2.5 nanometers . The substrate according to claim 1, wherein the hydrophobic linking layer has a thickness of 2.5 nanometers to 1 micrometer . The substrate according to claim 1, wherein the hydrophobic linking layer has a thickness of 1 to 100 micrometers . a) a substrate comprising an additive mixture of a hydrophobic component comprising an unsaturated carboxylic acid amide and a solvent, wherein the additive mixture is chemically produced in the substrate during the production of the substrate. Combined,
b) The substrate characterized in that the unsaturated carboxylic acid amide of the hydrophobic component is hydrophobically bound to a biomimetic surfactant . The substrate of claim 10, wherein the concentration of the hydrophobic component in the additive mixture is 0.1 to 10 weight percent . The substrate of claim 10 , wherein the concentration of the additive mixture in the substrate is 1 to 30 weight percent . The solvent is tetrahydrofuran, dimethyl sulfoxide, ethanol, methanol, ethyl acetate, dimethylformamide, dimethylacetamito, dioxane, N-methylpyrrolidone, chloroform, hexane, heptane, cyclohexane, toluene, formic acid, acetic acid, dichloromethane, and mixtures thereof. The substrate according to claim 10 , wherein the substrate is selected from the group consisting of: The biomimetic surfactant is poly (N-vinyldextran aldonamide-co-N-vinylhexanoamide), poly (N-vinyldextran aldonamide-co-N-vinyldodecanoamide) (PNVDA-co- PNVL), poly (N-vinylhexylamine-co-N-vinylheparinamine) (PNVHA-co-PNVHep A), poly (N-vinylhexylamine-co-N-vinylheparinamine-co-N-vinylmaltono) Amide) (PNVHA-co-PN-VHepA-co-PNVM), and poly (N-vinyl-5-peptidyl-pentylamine-co-N-vinyldextranaldoneamine-co-N-vinylhexylamine) (PVAm ( The substrate according to claim 10, which is selected from the group consisting of Pep: Dex: Hex)) . A method of increasing the hydrophobicity of a surface of a substrate to enhance the adhesion of a biomimetic surfactant polymer to the surface of the substrate, the method comprising the following steps:
a) preparing a substrate having a hydrophobic surface;
b) applying a hydrophobic linking layer comprising a hydrophobic component containing an unsaturated carboxylic acid amide to the surface of the hydrophobic substrate;
c) Step of applying the biomimetic surfactant polymer on the upper surface of the hydrophobic linking layer
Including,
d) the unsaturated carboxylic amide in the hydrophobic material is hydrophobically bonded to the surface of the hydrophobic substrate along the bottom surface of the tie layer, and the unsaturated in the hydrophobic material. A method for increasing the hydrophobicity of a substrate surface, wherein the carboxylic acid amide is hydrophobically bonded to the biomimetic surfactant along the upper surface of the linking layer . The method of claim 15, wherein the tie layer comprises a mixture of erucamide and a solvent . The solvent is from tetrahydrofuran, dimethyl sulfoxide, ethanol, methanol, ethyl acetate, dimethylformamide, dimethylacetamide, dioxane, N-methylpyrrolidone, chloroform, hexane, heptane, cyclohexane, toluene, formic acid, acetic acid, dichloromethane, and mixtures thereof. The method of claim 16, wherein the method is selected from the group consisting of: 16. The substrate material of claim 15 , wherein the substrate material is selected from the group consisting of silicone, polyurethane, polyether block amide (PEBA), polycarbonate, stainless steel, titanium, gold, platinum, palladium, and silver . Method. 16. The method of claim 15 , wherein the substrate surface is a surface selected from the group of medical devices consisting of pacemakers, defibrillators, neurostimulators, inserters, leads, catheters and stents. . The biomimetic surfactant is poly (N-vinyl dextran aldonamide-co-N-vinylhexanoamide), poly (N-vinyl dextran aldonamide) (PNVDA-co-PNVH), poly (N-vinyl dextran). Aldonamide-co-N-vinyldodecanoamide) (PNVDA-co-PNVL), poly (N-vinylhexylamine-co-N-vinylheparinamine) (PNVHA-co-PNVHep A), poly (N-vinyl) Hexylamine-co-N-vinylheparinamine-co-N-vinylmaltonamide) (PNVHA-co-PN-VHepA-co-PNVM), and poly (N-vinyl-5-peptidyl-pentylamine-co-N 16. The method of claim 15 , wherein the method is selected from the group consisting of -vinyldextran aldoneamine-co-N-vinylhexylamine) (PVAm (Pep: Dex: Hex)) . The substrate according to claim 10, wherein the hydrophobic component comprises erucic acid amide . a) a hydrophobic substrate surface;
b) a hydrophobic tie layer made of a hydrophobic material containing an unsaturated carboxylic acid amide;
c) a substrate containing a biomimetic surfactant containing an alkyl chain, wherein the hydrophobic linking layer is between the surface of the hydrophobic substrate and the biomimetic surfactant. Located,
d) the unsaturated carboxylic acid amide in the hydrophobic material of the hydrophobic tie layer is hydrophobically bonded to the hydrophobic substrate surface along the bottom surface of the tie layer; and
e) the unsaturated carboxylic amide in the hydrophobic material of the hydrophobic tie layer hydrophobically binds to the alkyl chain of the biomimetic surfactant along the top surface of the tie layer, thereby A substrate characterized in that a hydrophobic bond is formed between the surface of the hydrophobic substrate and the biomimetic surfactant . 23. A substrate according to claim 22, wherein the hydrophobic material comprises erucic acid amide . The biomimetic surfactant is poly (N-vinyldextran aldonamide-co-N-vinylhexanoamide), poly (N-vinyldextran aldonamide-co-N-vinyldodecanoamide) (PNVDA-co- PNVL), poly (N-vinylhexylamine-co-N-vinylheparinamine) (PNVHA-co-PNVHep A), poly (N-vinylhexylamine-co-N-vinylheparinamine-co-N-vinylmaltono) Amide) (PNVHA-co-PN-VHepA-co-PNVM), and poly (N-vinyl-5-peptidyl-pentylamine-co-N-vinyldextranaldoneamine-co-N-vinylhexylamine) (PVAm ( The substrate according to claim 22, wherein the substrate is selected from the group consisting of Pep: Dex: Hex)) . 23. A substrate according to claim 22, wherein the substrate material is selected from the group consisting of silicone, polyurethane, polyether block amide (PEBA) and polycarbonate . 23. The surface of claim 22, wherein the substrate surface is a surface selected from the group of medical devices consisting of pacemakers, defibrillators, neurostimulators, inserters, leads, catheters and stents. Base material.

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